Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 03 28 1 7 Zahra Eslami Department of Clinical Biochemistry, Hamadan University of Medical Science, Hamadan, Iran Seyed Javad Mirghani Shahid Mirghani Research Institute, Gorgan, Golestan, Iran Abdorreza Eghbal Moghanlou Department of Coaching Education, High School of Physical Education and Sports, Istanbul Esenyurt University, Istanbul, Turkey Mahbanou Ghaderi Department of Sport Science, Nahavand Higher Education Complex, BU-Ali Sina University, Hamedan, Iran 2025 07 02 2025 11 14 SARS-CoV-2 infection causes significant acute and long-term morbidity, including persistent pulmonary and muscular dysfunction in athletes. Physical exercise alters circulating microRNA (miR) profiles, and specific microRNAs have documented roles in inflammation, immune regulation, muscle metabolism, and regeneration. This study characterizes circulating microRNAs relevant to COVID-19 pathogenesis and post-viral recovery, including miR-155, miR-146a, the let-7 family, miR-21, miR-424, miR-1, miR-133, miR-499, miR-208, miR-486, and miR-22, and examines how different exercise modalities may modulate these microRNAs to support pulmonary and muscular function in post-COVID-19 athletes. miR-155 and miR-146a are highlighted as modulators of innate and adaptive inflammatory signaling and as mediators of cytokine responses implicated in severe COVID-19. Moreover, several microRNAs, such as miR-21, miR-155, miR-146a, and the let-7 family, converge on NF-κB and related pathways, linking altered miR expression to immune dysregulation and cytokine-driven tissue injury. Additionally, muscle-enriched and metabolism-associated microRNAs regulate myogenesis, mitochondrial biogenesis, and key metabolic pathways (PGC-1α, AMPK, mTOR)-processes essential for muscle repair, endurance recovery, and respiratory muscle support after SARS-CoV-2 infection. Different types of exercise produce distinct miR signatures; notably, moderate-intensity exercise consistently promotes anti-inflammatory and pro-repair miR patterns. We emphasize the therapeutic potential of moderate-intensity exercise as a non-pharmacological strategy to regulate miR expression, reduce cytokine-mediated damage, and support functional recovery in post-COVID-19 athletes. To our knowledge, this is the first study to link exercise-driven miR changes with functional pulmonary and muscular recovery in athletic populations recovering from COVID-19, supporting moderate-intensity exercise as a promising strategy for rehabilitation and performance restoration. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4505 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4505/2317

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 35 EN Asieh Emami Nejad Department of Biology, Payame Noor University, Tehran, Iran Saham Shaverdi Department of Biology, Payame Noor University, Tehran, Iran Marjan Taherian Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran Azim Forouzan Department of Gastroenterology and Hepatology, Clinical Research Development Unit, Amiralmomnin Hospital, School of Medicine, Arak University of Medical Sciences ,Arak, Iran Ali Sadoogh Abbasian Department of Nephrology, Clinical Research Development Unit of Amiralmomnin Hospital, School of Medicine, Arak University of Medical Sciences ,Arak, Iran Mohammadreza Rohani Department of Gastroenterology and Hepatology Internal Medicine, School of Medicine, Saveh University of Medical Sciences, Saveh, Iran Mojtaba Ahmadlou Department of Biostatistics, Clinical Research Development Unit of Amiralmomnin Hospital, School of Medicine, Arak University of Medical Sciences ,Arak, Iran Sayed Mohammad Matin Ishaghi Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Elnaz Sheydaee Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran Simin Najafgholian Department of Emergency Medicine, Clinical Research Development Unit, Valiasr Hospital, Arak University of Medical Science, Arak, Iran Mostafa Manian Department of Medical Laboratory Science, KerMS.C., Islamic Azad University, Kermanshah, Iran 2025 08 20 2025 12 01 Chimeric antigen receptor–natural killer (CAR-NK) cell therapy holds significant promise for cancer immunotherapy due to its efficient recognition and lysis of malignant cells. Despite the potential of CAR-NK therapy as a safer and more effective immunotherapeutic strategy, researchers are actively focusing on addressing its limitations. These include enhancing persistence, optimizing genetic engineering methods, and standardizing the production process for wider clinical applicability. The development of novel generations of CAR-NK cells, combined with a deeper understanding of their behavior in solid tumors, could potentially revolutionize cancer cell therapy and improve patient outcomes in the near future. However, to improve clinical outcomes and facilitate the broader application of CAR-NK cell therapies, we must address challenges related to the optimization of CAR constructs, in vivo persistence, tumor penetration, safety, and regulatory considerations. Overall, the article presents an extensive review of the challenges and potential strategies for improving the long-term antitumor efficacy of CAR-NK cell therapy, emphasizing the importance of combination therapies, drug delivery methods, and immune checkpoint blockade in enhancing the effectiveness of NK cell–based immunotherapy. The paper provides valuable insights into the intricate mechanisms and potential future applications of these strategies in cancer immunotherapy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4558 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4558/2324

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 16 EN Reyhaneh Sowti Clinical Research Development Unit, Imam Reza General Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Farzad Najafipour Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Sevil Ghaffarzadeh Rad Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hakimeh Ghorbani Department of Medical Biotechnology, Zanjan University of Medical Sciences, Zanjan, Iran Halimeh Amirazad Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2025 04 12 2025 12 01 The management of treatment strategies in COVID-19 is critical, especially in patients with type 2 diabetes. Non-enzymatic glycation of transmembrane protease serine 2 and angiotensin-converting enzyme 2 during COVID-19 in patients with diabetes may exacerbate immune dysregulation and inflammation. Elevated inflammatory cytokines such as IL-1, IL-2, IL-6, IL-7, and IL-10, tumor necrosis factor-α, interferon-γ, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1 have been observed in COVID-19 patients. This review aims to assess the relationship between inflammatory markers, including C-reactive protein, and micronutrients (vitamins D and C, zinc, and copper) with the severity of COVID-19 infection in patients with type 2 diabetes. A narrative review was conducted through a comprehensive literature search of English-language articles published between 2000 and 2025. The databases searched included PubMed, Scopus, the ISI Web of Science, Cochrane, and Embase. Search terms included COVID-19, infections, type 2 diabetes mellitus, interleukins, and micronutrients. English-language scientific articles, systematic reviews, and meta-analyses were included, while studies lacking sufficient information, letters, comments, and editorials were excluded. Evidence suggests that immune-boosting components such as proteins, vitamins, and minerals can enhance immunity to infections. Vitamins D and C, zinc, and copper play supportive roles in immune function, potentially modulating the inflammatory response in COVID-19 patients with type 2 diabetes. High levels of inflammatory cytokines correlate with increased disease severity in this population. Understanding the interplay between inflammatory markers and micronutrients may guide improved therapeutic strategies for managing COVID-19 in diabetic patients. Further research is warranted to clarify these relationships and optimize clinical outcomes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4416 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4416/2327

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 31 1 12 Yiwei Xu The First Clinical Medical College of Nanjing University of Traditional Chinese Medicine, Nanjing, China AND Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China Xiaohu Chen Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China 2026 01 28 2026 02 16 Coronary heart disease (CHD) is frequently accompanied by anxiety and depression, conditions that markedly worsen cardiovascular outcomes. Increasing evidence indicates that immune dysregulation, driven by gut microbiota alterations, plays a central role in linking psychological disorders with cardiovascular pathology through the gut–brain–cardiovascular axis. This narrative review systematically summarizes recent advances in the immunological mechanisms underlying CHD complicated by anxiety and depression. We focus on gut microbiota–immune interactions, inflammatory signaling pathways, immune-related microbial metabolites, and neuroimmune communication that collectively shape cardiovascular and mental health. Relevant studies addressing immune biomarkers, cytokine profiles, intestinal barrier dysfunction, and immune-modulating therapeutic strategies were critically analyzed. Gut microbiota dysbiosis contributes to intestinal barrier impairment and translocation of microbial products, leading to activation of innate and adaptive immune responses. Elevated pro-inflammatory cytokines, including interleukin 6 and tumor necrosis factor α, serve as key mediators linking systemic inflammation with atherosclerosis and neuropsychiatric symptoms. Microbial metabolites, such as trimethylamine N-oxide, exacerbate immune-driven vascular inflammation, whereas short-chain fatty acids exert immunoregulatory and anti-inflammatory effects. Neuroimmune mechanisms, including hypothalamic–pituitary–adrenal (HPA) axis activation and immune modulation of autonomic function, further integrate psychological stress with cardiovascular immune injury. Immune dysregulation represents a unifying mechanism connecting gut microbiota imbalance, neuropsychiatric disorders, and coronary heart disease. Targeting immune–microbiota interactions within the gut–brain–cardiovascular axis may offer novel diagnostic biomarkers and immunomodulatory therapeutic strategies for CHD patients with comorbid anxiety and depression. This immunological perspective provides a translational framework for future research and integrated clinical management. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4742 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4742/2352

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 1 9 EN Mohammad Hasan Bemanian Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Mojtaba Ranjbar Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Somayeh Heidary Ghadikolaii Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Saman Tavakoli Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Seyedehshabnam Seyedsalehi Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2025 07 17 2025 09 12 Ataxia Telangiectasia (AT) is a rare autosomal recessive disease with features of progressive cerebellar atrophy, immunodeficiency, and enhanced cancer susceptibility due to mutations in the ataxia telangiectasia mutated (ATM) gene. However, despite evidence from patients with AT in consanguineous Iranian families, limited information is still available on the genotype-phenotype association. This paper presents a familial case series of AT in Yazd, Iran, with a novel homozygous ATM mutation. This report examines a consanguine family in Yazd, Iran, with four members presenting with symptoms characteristic of AT, including progressive neurological decline, cerebellar atrophy, immunodeficiency, elevated alpha-fetoprotein, and recurrent infections. Genetic analysis confirmed a novel homozygous mutation of the ATM gene (c.1834C>A; p.Leu612Ile), which is a non-conservative substitution. It is predicted to result in loss of function, and parents were carriers of the mutation. Treatment included intravenous immunoglobulin, prophylactic antibiotics, and supportive care. One of the patients died due to severe infection despite intervention. This case series highlights the impact of consanguinity on the occurrence of AT and the supporting role of genetic testing in diagnosing ATM mutations. The results emphasize the need for improved genetic counseling, family planning, early immunological therapy, and culturally tailored public health strategies to effectively manage AT in consanguineous populations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4517 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4517/2288

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 19 1 12 EN Davood Mansouri Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Payam Tabarsi Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Somaye Jahanabadi Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Marjan Hemmatian Infectious Diseases and Tropical Medicine, Loghman Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Moradi Iran University of Medical Sciences, Tehran, Iran 2025 10 01 2025 11 14 Good’s syndrome (GS) is a rare immunodeficiency disorder associated with thymoma, characterized by hypogammaglobulinemia and impaired cellular immunity. Due to its variable clinical presentation and lack of clear diagnostic criteria, GS is often underrecognized or diagnosed with delay. We report 7 patients diagnosed with GS, including 2 previously reported cases and 5 new cases. Clinical, immunological, and radiological data were analyzed to characterize the spectrum of disease manifestations and outcomes. The study comprised 6 men and 1 woman, with a mean age of 48 years at thymoma diagnosis and 50 years at immunodeficiency detection. Two patients were diagnosed with thymoma and immunodeficiency simultaneously, while in 5 patients thymoma preceded GS diagnosis by 1 to 2.5 years. Common clinical features included recurrent sinopulmonary infections and autoimmune manifestations, such as myasthenia gravis and lichen planus. Opportunistic infections, including cytomegalovirus and mycobacterial infections were observed. Immunological profiles demonstrated hypogammaglobulinemia, reduced B-cell markers (CD19, CD20), and variable T-cell subsets. Intravenous immunoglobulin replacement therapy led to clinical improvement in most cases. Two patients succumbed to complications related to severe infections. GS presents with diverse clinical and immunological features, necessitating a high index of suspicion in patients with thymoma and recurrent infections. Early recognition and individualized immunoglobulin replacement therapy are critical for improving outcomes. Our series highlights the need for ongoing monitoring and management of immunodeficiency in thymoma patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4606 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4606/2328

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2025 12 22 1 10 EN Sepideh Mokabberi Department of Molecular Cell Biology and Genetics, Bu.C., Islamic Azad University, Bushehr, Iran Nahid Babaei Department of Molecular Cell Biology and Genetics, Bu.C., Islamic Azad University, Bushehr, Iran Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical sciences, Tehran, Iran Gholamreza Farnoosh Applied Biotechnology Research Centre, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 04 04 2025 09 11 Lung cancer remains a major cause of cancer-related mortality worldwide, with current treatments such as surgery, chemotherapy, and immunotherapy facing limitations, including severe side effects and high costs. Hyperthermia (H) has emerged as a promising strategy to enhance tumor sensitivity to treatments and reduce toxicity. This study investigates the effects of H in enhancing the anti-tumor efficacy of pemetrexed (PEM) and altering the expression profile of hsa-MiR-548c-3p (tumor suppressor) in the A549 cell line. A549 cells were cultured in DMEM medium and divided into four groups: Control, and treatment with H, PEM, and a combination of H and PEM. Subsequently, cell viability, apoptosis percentage, release rate of LDH, production of ROS, and the expression level of hsa-MiR-548c-3p, CASP 8 and 9, and TYMS genes were measured. Results revealed that the combination of H and PEM treatment had greater antitumor effects compared to the other groups. The combination of H and PEM significantly reduced cell viability, increased the percentage of apoptosis, LDH release, and ROS production, and upregulated hsa-MiR-548c-3p, CASP 8, and 9, while downregulating TYMS. The findings suggest that H enhances the chemotherapeutic efficacy of PEM by upregulating hsa-MiR-548c-3p expression and promoting apoptosis in lung cancer cells, making it a promising complementary approach for overcoming drug resistance. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4406 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4406/2276

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 06 1 16 Ying Li Department of Anesthesiology, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China Yanchun Tian Operating Room, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China Jing Gao Operating Room, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China Chuanying Dong Department of Anesthesiology, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China Xiaonan Chu Department of Anesthesiology, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China 2025 04 27 2025 08 31 This study aimed to investigate whether propofol-remifentanil anesthesia offers superior perioperative outcomes compared to propofol-fentanyl in pancreatic cancer surgery patients, with a focus on its effects on apoptotic molecules, plasma CXCL10/CXCL13 levels, and postoperative recovery. A total of 150 pancreatic cancer patients were divided into 2 cohorts receiving either propofol-fentanyl (control group, n=75) or propofol-remifentanil (study group, n=75) anesthesia. We measured perioperative hemodynamics (cardiac index [CI], mean arterial pressure [MAP], heart rate [HR]), T-cell subsets, postoperative recovery indices (eye-opening time, extubation time, spontaneous respiration recovery time), sedation and analgesia levels (via Ramsay sedation score [RSS] and visual analog scale [VAS]), plasma CXCL10/CXCL13 levels, and apoptosis-related proteins (Survivin, Bax, Caspase-4, Bcl-2) using enzyme-linked immunosorbent assays (ELISAs). Adverse reactions were also recorded. The study group exhibited significant advantages in hemodynamic stability and immune preservation. Despite similar baseline cardiovascular parameters, the remifentanil group maintained better CI, MAP, and HR stability during and after surgery. Flow cytometry analysis revealed better preservation of T-cell immunity (CD4+, CD3+, CD4+/CD8+ T cells) at 24 hours post-surgery. The intervention group also demonstrated accelerated postoperative recovery with significantly reduced emergence times (eye-opening, extubation, spontaneous respiration). Notably, the study group had more favorable inflammatory profiles (lower CXCL10/CXCL13 levels) and enhanced apoptotic responses (modulated Bax, Caspase-4, Survivin, and Bcl-2 expression). Clinical outcomes were superior in the study group, with significantly fewer adverse events (2 vs. 9 patients). Propofol-remifentanil anesthesia provides effective sedation and analgesia in pancreatic cancer surgery, modulates key biological pathways related to apoptosis and inflammation, and improves postoperative recovery. These findings suggest that the choice of anesthesia regimen may have significant implications for perioperative outcomes and potentially long-term prognosis in pancreatic cancer patients. Future research should further explore the underlying mechanisms and long-term clinical benefits of this anesthesia strategy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4425 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4425/2279

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 1 10 Mohsen Ghoryani Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran Soroush Gorgani Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mahdi Atabaki Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Elmira Noori Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Zhaleh Shariati-Sarabi Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mojgan Mohammadi Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran 2025 10 17 2025 11 09 Osteoarthritis (OA) is the most common form of arthritis, characterized by pathological changes in joint components. Increasing evidence suggests that helper T (TH) lymphocytes play a pivotal role in the inflammatory processes associated with OA. Curcumin, the primary polyphenolic compound found in Curcuma longa, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of curcumin on the gene expression of key transcription factors of TH1 and TH2 cells and to explore their associations with clinical and immunological parameters in patients with knee OA. This mechanistic sub-study presents a secondary molecular analysis of RNA biospecimens from a previously completed double-blind, placebo-controlled clinical trial involving 30 patients with knee OA. Participants were randomly assigned to receive either 80 mg/day of nano-micelle curcumin or a placebo for 3 months. Expression levels of T-box transcription factor 21 (T-bet) and GATA binding protein 3 (GATA3), the key transcription factors of TH1 and TH2 cells, respectively, were quantified using SYBR Green-based real-time PCR. Their associations with changes in visual analogue scale (VAS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and percentages of CD4+ and CD8+ T cells were analyzed. Curcumin administration significantly reduced T-bet gene expression compared to baseline and showed a positive correlation with the frequency of CD8+ T cells, while GATA3 expression remained unchanged. These findings may provide a novel molecular perspective on curcumin's potential to influence CD8+ T cell dynamics by modulating TH1-associated transcriptional programs. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4633 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4633/2284

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 1 19 Danxi Wang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Renxia Zhang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Huili Huang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Ling Yin Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China 2025 05 20 2025 09 12 Non-alcoholic fatty liver disease (NAFLD) is a major hepatic manifestation of metabolic syndrome and encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). This study aimed to evaluate the contribution of immunological, inflammatory, and metabolic parameters-including cytokine levels, immune cell profiles, and microRNA (miR) expression-in the progression from NAFLD to NASH among individuals with features of metabolic syndrome. An observational study was conducted between January 2022 and December 2024, enrolling 300 adult patients with radiologically or histologically confirmed NAFLD. Patients underwent comprehensive anthropometric, biochemical, and immunological assessments, including cytokine profiling (interleukin [IL]-6, IL-17, tumor necrosis factor-α [TNF-α], transforming growth factor-β1 [TGF-β1]), immune cell phenotyping (T helper 17 [TH17], regulatory T cells [Tregs], monocytes), and miR quantification (miR-122, miR-34a). Liver biopsy was performed in 95 selected cases.. The nursing team also assists in coordinating multidisciplinary care and ensuring follow-up compliance, which are vital for long-term disease management and reducing progression to NASH. Significant elevations were observed in metabolic parameters (body mass index [BMI], homeostatic model assessment for insulin resistance [HOMA-IR]), hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], ferritin), and oxidative stress markers (malondialdehyde [MDA]). Adipokines (↑leptin, ↓adiponectin), hepatokines (↑fibroblast growth factor 21 [FGF21], ↑fetuin-A), and cytokines (↑IL-6, ↑TNF-α, ↑IL-17) were markedly altered in patients with biopsy-proven NASH. This study reinforces that pro-inflammatory cytokines, altered immune cell profiles, and dysregulated miRs serve as promising biomarkers for early identification and potential therapeutic targeting in metabolic syndrome-associated steatohepatitis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4449 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4449/2285

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 1 11 EN Serkan Filiz Department of Pediatric Allergy and Immunology, Training and Research Hospital, Antalya, Türkiye Güney Külice Department of Pediatric Allergy and Immunology, Training and Research Hospital, Antalya, Türkiye Zeycan Canıtez Oral Department of Pediatric Allergy and Immunology, Training and Research Hospital, Antalya, Türkiye Şennur Keleş Department of Pediatric Allergy and Immunology, Training and Research Hospital, Antalya, Türkiye Dilek Yapar Turkish Ministry of Health, Muratpaşa District Health Directorate, Antalya, Türkiye Osman Keysan Turkish Ministry of Health, Emergy Ambulance Servise Directorate, Antalya, Türkiye Mehmet Gülşen Turkish Ministry of Health, Emergy Ambulance Servise Directorate, Antalya, Türkiye Ahu Sezgin Turkish Ministry of Health, Emergy Ambulance Servise Directorate, Antalya, Türkiye 2025 07 22 2025 10 27 Anaphylaxis is a severe, rapidly progressing, and potentially life-threatening emergency requiring prompt, evidence-based intervention. This study assessed pre-hospital emergency healthcare professionals’ knowledge of anaphylaxis diagnosis, acute management, and treatment protocols in line with current clinical guidelines. A descriptive cross-sectional study was conducted between February and April 2025 among physicians, paramedics, and emergency medical technicians (EMTs) working in Emergency Medical Services (EMS) stations. Data were collected via a 21-item Google Forms survey covering demographics and key knowledge domains based on established pediatric anaphylaxis guidelines. A total of 322 professionals participated: paramedics (n = 214, 66.5%), EMTs (n = 73, 22.7%), and physicians (n = 35, 10.9%). Although most reported prior anaphylaxis training (90.0%) and clinical encounters (87.6%), only 52.2% correctly identified all three diagnostic criteria. Regarding pharmacologic management, 81.7% recognized epinephrine as first-line treatment, with physicians performing best (94.3%) compared to paramedics (81.8%) and EMTs (75.3%). Similarly, 81.1% correctly identified the intramuscular route, with physicians again demonstrating superior knowledge (95.5%). However, major deficiencies were noted in appropriate patient positioning (52.2%) and epinephrine auto-injector use (50.6%), with significant inter-professional differences across both domains. Substantial knowledge gaps exist among pre-hospital emergency providers regarding anaphylaxis diagnosis, patient positioning, and auto-injector administration. Targeted training and standardized protocols are urgently needed to enhance competency and improve patient safety in pre-hospital anaphylaxis management. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4529 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4529/2287

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 28 1 12 Omid Sadatpour Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Amirreza Azimi Department of Neurology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Zahra Salehi Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran AND Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran Mohammad Javad Tavassolifar Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Ali Akbar Saboor-Yaraghi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Maryam Izad Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran 2025 08 31 2025 09 06 Chemokines and their receptors play a central role in mediating the migration of pathogenic T cells into the central nervous system of patients with multiple sclerosis (MS). Vitamin D and curcumin are known to possess anti-inflammatory and immunomodulatory properties; however, their combined effects on T-cell chemokine receptor expression in MS remain poorly defined. In this study, we investigated the in vitro effects of vitamin D, curcumin, and their combination on CD4+ and CD8+ T cells expressing CXCR3, CCR6, and CCR4 in patients with relapsing-remitting MS (RRMS). Peripheral blood mononuclear cells were collected from patients in relapse (n=10), remission (n=14), and healthy controls (n=15) and analyzed using flow cytometry. Relapse patients exhibited elevated frequencies of CXCR3+CD4+ T cells compared to healthy controls, which normalized following treatment. Increased CCR6+CD4+ T cells and CXCR3+CD8+ T cells were also observed in patients, with a significant reduction achieved only after combined treatment with vitamin D and curcumin. The combined treatment further decreased the mean fluorescence intensity of CXCR3 and CCR6 on T cells in relapse patients, while vitamin D alone specifically reduced CCR4+CCR6+CD4+ T cells, a TH17-like subset enriched during relapse. These findings indicate that vitamin D and curcumin, particularly in combination, modulate T-cell activity by downregulating chemokine receptor expression and may represent a promising adjunctive approach for controlling immune cell migration in MS. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4568 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4568/2289

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 9 EN Jafar Salimian Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Soheil Vazifedust Solid Tumor Research Centre, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences,Urmia,Iran Majid Mirzaei Nodooshan Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 10 06 2025 11 07 Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that can progress to cirrhosis and liver failure if untreated. Current therapies, mainly corticosteroids, are effective but limited by adverse effects and incomplete responses, prompting the search for safer alternatives. Peiminine, an alkaloid derived from Fritillaria species, has demonstrated anti-inflammatory and antioxidant properties in several disease models. This study evaluated its efficacy in a concanavalin A (ConA)–induced mouse model of AIH. Male C57BL/6 mice were divided into six groups, including ConA-injured animals, and treatment groups receiving peiminine (3 mg/kg, i.p.), prednisolone (10 mg/kg, i.p.), or their combination. ConA injection caused sharp increases in ALT (↑ 5.4-fold), AST (↑ 4.8-fold), and ALP (↑ 3.9-fold), alongside marked elevations in MPO activity, nitric oxide, and pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ). Peiminine significantly reversed these alterations—reducing ALT, AST, and ALP by 65% to 75% and restoring IL-4, TGF-β, and SOD activity toward normal values. Pre-treatment provided stronger protection than post-treatment, and outcomes were comparable to those of prednisolone, with combination therapy yielding the greatest improvement across all indices. These findings indicate that peiminine mitigates immune-mediated hepatic injury by modulating cytokines, reducing oxidative stress, and maintaining liver integrity. Peiminine may represent a promising preventive or adjunct therapy for AIH, warranting further mechanistic and long-term investigations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4610 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4610/2290

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 17 Chunli Mei Department of Dermatology, Deqing County People's Hospital, Deqing County, China Chunye Xu Department of Endocrinology, Deqing County People's Hospital, Deqing County, China Zhibin Yu Department of Dermatology, Deqing County People's Hospital, Deqing County, China Lihong Shen Department of Orthopaedics, Deqing County People's Hospital, Deqing County, China 2025 08 29 2025 09 15    Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous immune dysregulation. Although interleukin-17 (IL-17) signaling is implicated in AD, IL-17-related diagnostic biomarkers and molecular subtypes remain unclear. This study aimed to identify IL-17-associated biomarkers, characterize immune infiltration and subtypes, and explore upstream regulatory mechanisms. Gene expression datasets (GSE121212, GSE6012) were acquired from the Gene Expression Omnibus database, and an IL-17-related gene set was collected from the Gene Set Enrichment Analysis website (GSEA)(http://www.gsea-msigdb.org/gsea/msigdb/search.jsp). Differential expression (limma) and Weighted Gene Co-expression Network Analysis were integrated to identify candidate genes, followed by feature selection using Least Absolute Shrinkage and Selection Operator and random forest. We evaluated immune cell infiltration by applying the CIBERSORT algorithm alongside single-sample Gene Set Enrichment Analysis. GSEA was applied to investigate underlying biological processes. AD patients were clustered into subtypes relying on IL-17 scores using ssGSEA. Our integrated analysis identified IL4R and PRSS22 as key IL-17-related diagnostic biomarkers for AD, demonstrating excellent diagnostic accuracy across both training and validation cohorts. Immune-infiltration analyses revealed altered immune-cell composition and correlations observed between the identified biomarkers and specific immune cells. Two distinct AD subtypes were identified based on IL-17 scores, exhibiting immune infiltration patterns and enriched biological pathways. A ceRNA network highlighted potential regulatory mechanisms involving these biomarkers. IL4R and PRSS22 are robust IL-17-related diagnostic biomarkers for AD, with high predictive power across cohorts. Immune infiltration profiling and IL-17 score-based subtyping reveal AD heterogeneity. These findings provide a foundation for improved diagnosis, molecular stratification, and potential therapeutic targeting in AD. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4567 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4567/2294

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 12 Guimin Zheng Department of General Medicine, Hebei General Hospital, Shijiazhuang, Hebei Province, China Lei Wang Department of Medical Imaging, Hebei General Hospital, Shijiazhuang, Hebei Province, China Jingjing Cao Department of General Medicine, Hebei General Hospital, Shijiazhuang, Hebei Province, China Xiao Zheng Department of Rheumatology, Hebei General Hospital, Shijiazhuang, Hebei Province, China 2025 08 13 2025 11 05 Cognitive dysfunction (CD) is a common neuropsychiatric manifestation of systemic lupus erythematosus (SLE), but its early identification lacks objective serological markers. This study aimed to explore the predictive value of combined serum interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and neurofilament light chain (NfL) for CD in SLE patients. A total of 108 SLE patients (January 2018–December 2019) and 50 healthy controls were enrolled. SLE patients were divided into CD group (MoCA score <26, n=49) and non-CD group (MoCA score ≥26, n=59). Serum IL-6, ICAM-1, and NfL levels were detected by ELISA. Logistic regression and ROC curve analyses were performed to evaluate risk factors and predictive efficacy. Serum IL-6, ICAM-1, and NfL levels were significantly higher in SLE patients than in controls (p<0.05), and further elevated in the CD group. These three markers were independent risk factors for SLE-related CD. The AUC of combined detection (0.852) was significantly higher than individual markers (0.734, 0.712, 0.677). Serum IL-6, ICAM-1, and NfL have certain predictive value for CD in SLE patients, and the combined detection of these three indicators offers higher predictive value. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4551 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4551/2295

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 11 1 13 Pouria Ghiaee Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Sarehsadat Ebrahimi Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman, Iran Seyed Alireza Mahdaviani Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Tarighat Monfared Pediatric Respiratory and Sleep Medicine Research Center, Children’s Medical Center Hospital, Tehran Universityof Medical Sciences, Tehran, Iran Marzieh Tavakol Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran Mehrdad Dargahi Mal-Amir Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Center, Ahvaz, Iran Nima Rezaei Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran Abdollah Jafarzadeh Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran 2025 03 15 2025 08 31 Common variable immunodeficiency disease (CVID) is the most prevalent symptomatic inborn errors of immunity, determined by defective B cell function, impaired antibody production, and susceptibility to frequent respiratory infections, enteropathy, autoimmunity, and malignancy. Due to the importance of autoimmunity in CVID and the probable role of regulatory B lymphocytes, we aimed to determine the frequency of B10 cells in CVID patients with and without autoimmunity. A total of 24 CVID patients and 12 healthy controls were enrolled in the study. Patients were divided into two equal groups, with and without autoimmunity. Peripheral blood cells were stained with monoclonal antibodies (mAbs) to identify CD24hiCD38hi B cells, CD27int CD38+ (plasmablasts), and CD24hiCD27+ B cells by flow cytometry. The percentages of B10, CD24hiCD27+ and CD27int CD38+ cells were significantly lower in total CVID patients, CVID patients with autoimmunity and CVID patients without autoimmunity compared to healthy controls (mean±standard deviation (SD) percentage of B10 cells: 6.36±9.21(total CVID), 2.81±5.00 (CVID with autoimmunity), and 3.25±3.5 (CVID without autoimmunity) vs. 13.02±12.45 (healthy controls); CD24hiCD27+ cells: 2.39±3.89, 3±5.20 and 1.78±1.94 vs. 20.38±14.27; CD27int CD38+ cells: 6.80±18.49, 7.40±20.24 and 6.20±17.45 vs. 11.84±5.71). CVID patients without autoimmunity had a higher percentage of CD24hiCD38hi cells than CVID patients with autoimmunity (4.73±4.14 vs. 2.62±5.02). The defect of regulatory B cells plays a significant role in the pathogenesis of autoimmunity in CVID. Further multicenter studies with higher sample sizes are suggested to determine the role of Breg cells in the clinical course of autoimmunity.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4386 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4386/2306

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 11 1 17 EN Azadeh Roostaee Department of Biology, Marv.C., Islamic Azad University, Marvdasht, Iran Ramin Yaghobi Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Afsoon Afshari Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Mojtaba Jafarinia Department of Biology, Marv.C., Islamic Azad University, Marvdasht, Iran 2025 06 09 2025 11 09 Human cytomegalovirus (HCMV) is a frequent complication in kidney transplant recipients (KTRs), often impacting immune regulation. TH9 cells, a subset of CD4+ T cells, are characterized by their secretion of interleukin-9 (IL-9). This study aimed to analyze the phenotypic profile of TH9 cells and their associated cytokine expression in KTRs, and to evaluate mRNA levels of IL-4 and transforming growth factor-β (TGF-β), key cytokines involved in TH9 differentiation. Ten HCMV+ and 10 HCMV− KTRs, along with 10 age- and sex-matched healthy controls, were enrolled. HCMV viral load was quantified using TaqMan real-time polymerase chain reaction. Flow cytometry was used to assess surface markers (CCR6+CCR4−IL-4Rα+CD4+) and intracellular IL-9 expression in TH9 cells. Gene expression levels of IL-4 and TGF-β were also assessed. Surface staining revealed a significantly higher frequency of CD4+CCR4− and CD4+CCR6+ T cells in HCMV− KTRs compared to HCMV+ patients. Conversely, the overall frequency of CD4+ TH9 cells was elevated in HCMV+ KTRs. Intracellular staining demonstrated a significant increase in CD4+IL-9+ and CD4+IL-4Rα+ T cells in the HCMV+ group. Additionally, mRNA expression levels of IL-4 and TGF-β were markedly higher in HCMV+ KTRs than in HCMV− counterparts. These findings suggest a potential role for TH9 cells and their signature cytokine IL-9 in the antiviral immune response in KTRs. While TH9 cells may contribute to HCMV-related immune modulation, further research is needed to fully elucidate their protective mechanisms against viral infections.   Keywords: ; ; ;    https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4485 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4485/2308

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 20 1 9 EN Saeede Amani Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Respiratory Immunology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Basic Science, Ka.C, Islamic Azad University, Karaj, Iran Babak Salimi Research Center of Thoracic Oncology (RTCO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Shahrzad Ahmadi Respiratory Immunology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Mabani Research Center of Thoracic Oncology (RTCO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Ian Adcock Respiratory Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom Esmaeil Mortaz Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Respiratory Immunology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2025 05 25 2025 10 17 MicroRNAs (miRs) play a crucial role in the pathogenesis, progression, and prognosis of cancer, including non-small-cell lung cancer. The purpose of this present study was to investigate the correlation between ‎MIR141‎ expression in peripheral blood mononuclear cells and serum levels of interleukins (IL-6 and IL-8) and CXCL10 in non-small-cell lung cancer patients. Forty-six patients diagnosed with primary non-small-cell lung cancer and 30 age- and gender-matched healthy controls were recruited in this prospective cohort study. Two 3-mL samples of systemic blood were collected into tubes either containing or without an anticoagulant from all patients before treatment and from healthy controls. PBMCs were isolated, total RNA extracted, and microRNA expression measured using real-time quantitative polymerase chain reaction. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. MIR141‎ expression in peripheral blood mononuclear cells was significantly higher in non-small-cell lung cancer patients (4.124 [3.259–4.944]) compared to healthy controls (2.181 [1.036–2.946]). The area under the Receiver operating characteristic (ROC) curve, AUC for MIR141,‎ was 0.695 (95% CI, 0.603–0.787), indicating statistically significant diagnostic performance. Serum levels of IL-6, IL-8, and CXCL10 were also markedly elevated in non-small-cell lung cancer patients compared to healthy controls. Increased expression of MIR141 in peripheral blood mononuclear cells is associated with non-small-cell lung cancer and elevated systemic inflammatory mediators. These findings suggest that peripheral blood MIR141 may serve as a promising non-invasive biomarker for the diagnosis of non-small-cell lung cancer. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4184 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4184/2312

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 23 1 7 Amir Kahrizi Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Armin Akbar Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Ahmad Najafi Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Hossein Asgarian-Omran Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran Reza Valadan Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran Mohammad Mehri Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Mohsen Tehrani Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran 2025 06 02 2025 11 04 The Warburg effect is one of the most important metabolic alterations in tumor cells. Hypoxia-inducible factor 1-alpha (HIF-1α) targets a broad range of gene promoters in normoxic and hypoxic conditions in cancers. Herein, we investigate the effects of HIF-1α inhibition on cell viability and messenger RNA (mRNA) expression of immune checkpoint receptors (ICRs) in acute myeloid leukemia cell lines. K-562 and HL-60 cells were treated with silibinin as an HIF-1α inhibitor. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by quantification of V-domain immunoglobulin suppressor of T-cell activation (VISTA), T-cell immunoglobulin and mucin domain 3 (TIM3), and Galectin-9 mRNA expression via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expression levels of VISTA, TIM3, and Galectin-9 decreased after silibinin treatment within both K-562 and HL-60 cells; however, there were some disparities in gene expression levels between the two cell lines. VISTA and TIM3 expression were reduced by approximately 70% in K-562 at the 40% inhibitory concentration (IC40), while no significant changes were observed in HL-60 cells. Conversely, Galectin-9 expression was decreased significantly at both the IC30 and IC40 in HL-60, whereas it was almost consistent in K-562 cells.  Collectively, we have shown that silibinin could serve as a cytotoxic small-molecule inhibitor and regulate the expression of ICRs, potentially counteracting T-cell exhaustion. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4476 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4476/2314

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 03 12 1 13 Azizollah Yousefi Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Saeed Sepehry Vafa Department of Pediatrics, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran Mina Mirzad Department of Pediatrics, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran Fatemeh Elham Mahjoub Department of Pathology, School of Medicine, Maternal, Fetal, and Neonatal Research Center, Family Health Research Institute, Iran University of Medical Sciences, Tehran, Iran Behnam Shahsavand Department of Pediatrics, Ali-Asghar Children's Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Ebrahim Babaee Department of Community and Family Medicine, Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Fereshteh Karbasian Department of Pediatric Gastroenterology and Hepatology, Ali-Asghar Children's Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Nabavi Department of Allergy, Rasoul-e-Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Hasan Bemanian Department of Allergy, Rasoul-e-Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Sima Shokri Department of Allergy, Rasoul-e-Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Saba Arshi Department of Allergy, Rasoul-e-Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Morteza Fallahpour Department of Allergy, Rasoul-e-Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 2025 07 17 2025 09 12 Eosinophilic gastrointestinal diseases (EGIDs) are chronic, TH2-mediated conditions. Eosinophilic esophagitis (EoE) is the most common type, while non-EoE EGIDs affect other gut segments. This retrospective study of 111 patients (50 EoE and 61 non-EoE) from 2011 to 2022 compared the clinical aspects of these 2 types. Dysphagia and food impaction dominated in EoE, while abdominal pain, nausea, and diarrhea were more common in non-EoE EGIDs. Atopic comorbidities were frequent. Diagnostic delays>1 year were more common in EoE (72% vs 47.5%). The overall clinical response rate was 88.29%, with most patients using food avoidance (90.99%) and proton pump inhibitors (94.59%). Clinical relapses occurred in 38.88% over the mean follow-up of 4.62 years and were unaffected by therapy type. Failure to thrive was seen in 26.7%, with no significant intergroup difference. This study highlights a prolonged diagnostic delay in EoE vs non-EoE EGIDs. Both groups showed similar, favorable response rates, underscoring a need for greater awareness. Prospective studies with standardized measures are required to optimize management. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4520 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4520/2315

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 09 1 11 Jie Deng Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China Hongyi Liu Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China Yiran Zang Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China Zhihan Wei Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China Xue Yue Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China Zhanguo Jin Department of Otorhinolaryngology Head and Neck Surgery, Air Force Medical Center, PLA, Beijing, China 2025 07 31 2025 10 11 The research intended to elucidate the synergistic effects of Eosinophils (Eos) and mast cells (MCs) on human nasal epithelial cells (HNEpCs) in the context of allergic rhinitis (AR), focusing on inflammation, tight junction protein expression, and DNA damage. Cell proliferation capacity was measured using the CCK-8 method, apoptosis was examined via the TUNEL assay, and inflammatory cytokine levels were assayed via ELISA. Western blotting evaluated the protein abundance of tight junction proteins (ZO-1, Occludin) and CD40L/CD40. Immunofluorescence was used to detect γH2AX (DNA damage) as well as subcellular ZO-1/Occludin distribution. Co-immunoprecipitation (Co-IP) was used to analyze the CD40L-CD40 interaction between Eos and MCs. Eos and MCs significantly reduced HNEpC viability and enhanced apoptosis, with the most pronounced effects in the AR+Eos+MC group. Inflammatory cytokine levels were markedly elevated in the Eos+MC and AR+Eos+MC groups, with the highest concentrations observed in the AR+Eos+MC group. Western blot and immunofluorescence analyses showed decreased expression of ZO-1 and Occludin in treatment groups compared to Control, along with a shift in their localization from the cell membrane to the cytoplasm. γH2AX expression, indicating DNA damage, was significantly elevated, with the highest levels observed in the AR+Eos+MC group. Co-immunoprecipitation (Co-IP) analysis confirmed enhanced CD40L–CD40 interaction involving Eos and MCs within the Eos+MC and AR+Eos+MC groups. Eosinophils and mast cells synergistically promote inflammation, disrupt the nasal epithelial barrier, and exacerbate DNA damage. The CD40L-CD40 pathway serves an essential function in their interaction, providing a potential therapeutic target for AR. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4534 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4534/2318

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 11 Yan Kang Department of Oncology, Liangxiang Hospital of Beijing Fangshan District, Capital Medical University, Fangshan, Beijing, China Baocen Xu Department of Thoracic Surgery, Xing’an League People’s Hospital, Ulanhot, Xing’an League, Inner Mongolia Autonomous Region, China Siyu Wang Department of Oncology, Liangxiang Hospital of Beijing Fangshan District, Capital Medical University, Fangshan, Beijing, China Shaozhi Xi Department of Comprehensive Surgery, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China 2025 10 16 2025 12 15 Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) plays a pivotal role in tumor immune evasion. The efficacy of these treatments is limited by variable patient responses and adverse effects. It is necessary for a deeper understanding of the underlying biological mechanisms. This study used a 2-step Mendelian randomization (MR) approach to investigate causal relationships among gut microbiota, lipid and amino acid metabolic traits, and PD-1/PD-L1. The summary statistics for 412 traits of the gut microbiome (N=7738), 249 traits of serum metabolites (N=115 078), and 2 traits of PD-1/PD-L1 (N=3301) were derived from publicly genome-wide association studies. The primary method employed for MR was inverse-variance weighted regression. We conducted a series of sensitivity analyses to evaluate the reliability of the causal estimates. Subsequently, mediation analysis was undertaken to elucidate the pathway from gut microbiome to PD-L1, mediated by serum metabolic markers. Our analyses identified 28 gut microbial traits significantly affecting PD-L1 and 14 affecting PD-1, 8 of which remained consistently linked to PD-L1 after sensitivity analysis. Furthermore, 13 serum lipid and amino acid metabolic traits exhibited significant causal effects on PD-L1, with 6 remaining robust post analysis. Notably, Bacteroides dorei demonstrated a causal effect on PD-L1, mediated 9.6% by the metabolic biomarker phenylalanine. These findings highlight the intricate interplay among gut microbiome, metabolic biomarkers, and immune regulation. They suggest novel therapeutic targets for cancer treatment that emphasize the value of microbiome and metabolic biomarkers in improving immunotherapy outcomes and promoting personalized medicine. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4629 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4629/2322

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 13 Jun Zhang Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Huijing Tong Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Xiaojun Wang Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Yingwei Ding Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Linghong Xu Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Gang Chen Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China 2025 12 10 2026 01 27 Sepsis is a life-threatening systemic inflammatory response syndrome marked by high mortality and immune dysfunction. Histamine, synthesized from histidine, by histidine decarboxylase (HDC), regulates immune cell recruitment and inflammatory mediators, playing a key role in inflammatory diseases. The precise mechanisms and clinical significance of histamine in sepsis require further study. Gene expression data from the Gene Expression Omnibus (GEO) database were analyzed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed histamine-related genes (DEHRGs). Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), were utilized to screen diagnostic genes, and a predictive model was constructed and validated using receiver operating characteristic analysis and decision curve analysis (DCA). Functional enrichment, immune infiltration assessment, using single-sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), regulatory network construction, and drug prediction were subsequently conducted. Nine DEHRGs were identified. Three key diagnostic genes-FYN, IL2RB, and MMP8-were selected and validated across multiple cohorts, showing high diagnostic accuracy (area under the curve [AUC]>0.85). The study revealed distinct immune patterns, including increased regulatory T cell (Treg) infiltration in the sepsis group. Two sepsis molecular subtypes with differential immune characteristics were also identified. This study systematically explored the association between histamine and sepsis pathogenesis, defining a three-gene diagnostic model and elucidating complex immune and molecular regulatory mechanisms. These findings offer new insights for developing targeted diagnostic and therapeutic strategies for sepsis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4694 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4694/2323

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 21 1 21 Qiong Wei Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Chun Wang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Yi Yang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Yuping Li Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China Huan Huang Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China 2025 09 26 2026 01 27 Long noncoding RNA SSTR5 antisense RNA 1 (lncRNA SSTR5-AS1) is increased in a variety of tumors, but its molecular mechanism in ovarian cancer (OC) remains unreported. lncRNA SSTR5-AS1 and signal transducer and activator of transcription 3 (STAT3) expressions in SKOV3 and A2780 cells were interfered (n=3), and the cells were treated with ferroptosis inhibitor Ferrostatin-1. lncRNA SSTR5-AS1 and STAT3 expressions were discovered. The interaction between them was detected by immunoprecipitation assay. The cell malignant progression was evaluated through Transwell and scratch healing assays. Ferroptosis was measured through kits and fluorescent probes; the expression levels of immunosuppressive factors and STAT3/solute carrier family 7 member 11 (SLC7A11) signaling pathway were discovered through Western blot. A transplanted tumor model (n=6 mice per group) was established to evaluate ferroptosis, immunosuppressive factors, and tumor growth in tumor tissues. lncRNA SSTR5-AS1 was up-regulated on OC cells. LncRNA SSTR5-AS1 and STAT3 bind to each other, and knockdown of lncRNA SSTR5-AS1 can reduce p-STAT3/STAT3 and SLC7A11 protein levels (one-way ANOVA). Knocking down lncRNA SSTR5-AS1 and STAT3 suppressed cell viability, migratory rate, and invasive cell number; increased reactive oxygen species (ROS) and Fe2+ levels; and reduced immunosuppressive factors and ferroptosis proteins. Ferrostatin-1 significantly reversed the effect of knockdown of lncRNA SSTR5-AS1 on ferroptosis. In transplanted tumor tissues, downregulation of lncRNA SSTR5-AS1 can reduce tumor size and volume, show obvious iron deposition, and reduce the secretion of immunosuppressive factors. Knockdown of lncRNA SSTR5-AS1 induces ferroptosis and reduces the secretion of immunosuppressive factors through the STAT3/SLC7A11 pathway, thereby antagonizing OC. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4598 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4598/2329

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 26 1 16 Jianping Jiang Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Shumin Li Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Mengqing Cao Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Haiqin Wang Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Xiaoyan Jin Inpatient Service Center, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China 2025 08 20 2025 11 14 Bronchiectasis is a chronic respiratory condition characterized by persistent airway inflammation and recurrent infections, yet its underlying pathogenesis remains incompletely understood. This study aimed to investigate the roles of the lower respiratory tract microbiome and serum cytokine/chemokine profiles in the pathogenesis of bronchiectasis. In this retrospective study, we enrolled 285 bronchiectasis patients admitted to our hospital between January 2024 and June 2025. Participants were categorized into an acute exacerbation group (n=158) and a clinically stable group (n=127). We compared the two groups in terms of respiratory pathogens, immune function indicators (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, white blood cell count, and neutrophil count), pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A), anti-inflammatory cytokines (interleukin-10 and interleukin-4), acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A), and chemokines (monocyte chemoattractant protein-1). The involvement of these factors in disease pathogenesis was analyzed. Significant differences were observed between the groups in the rates of hypoalbuminemia, the presence of dyspnea and hemoptysis, and the oxygenation index in arterial blood gas analysis. Sputum cultures were positive in 103 (65.19%) patients in the acute exacerbation group, compared to 58 (45.67%) in the stable group. Immune markers CD3+, CD4+, CD8+, and the CD4+/CD8+ ratio were lower during acute exacerbation, while WBC and NEUT levels were elevated. Pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A) and acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A) were significantly higher during exacerbation, whereas anti-inflammatory cytokines (interleukin-10 and interleukin-4) were lower. Monocyte chemoattractant protein-1 levels were also elevated during exacerbation. Dysbiosis of the lower respiratory tract microbiome, immune dysfunction, and exacerbated inflammatory responses are interrelated and collectively contribute to the pathogenesis of bronchiectasis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4557 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4557/2330

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 26 1 11 Yafen Huang Department of Gynecology, Huangshi Maternity and Child Health Hospital, Huangshi, Hubei, China Wanfang Yang Department of Ultrasound Imaging, Huangshi Central Hospital, Huangshi, Hubei, China Shasha Wang Department of Gynecology, Huangshi Maternity and Child Health Hospital, Huangshi, Hubei, China Shuangxiang Yang Department of Gynecology, Huangshi Maternity and Child Health Hospital, Huangshi, Hubei, China 2025 10 15 2025 12 28 This study aimed to assess the clinical symptoms associated with UFs and to evaluate dynamic, longitudinal changes in serum inflammatory markers before and after treatment in women diagnosed with UFs compared with healthy controls. In this retrospective observational study, 90 women including 60 women diagnosed with UFs and 30 age-matched healthy controls. Uterine fibroids were confirmed by ultrasonography and histopathology. Serum levels of tumor necrosis factor α (TNF-α), interferon β (IFN-β), IFN-γ, C-reactive protein (CRP), and basic fibroblast growth factor (FGF) were measured using standardized enzyme-linked immunosorbent assay kits. Lymphocyte subsets were analyzed via flow cytometry. Patients with UFs underwent medical or surgical treatment based on clinical indications, and inflammatory markers were reassessed 3 months posttreatment. There were various symptoms such as pelvic pain (66.67%), abnormal bleeding (66.67%), organ-compression symptoms (45%), infertility (26.67%), and miscarriage (18.33%) compared with controls. Women diagnosed with UFs showed a higher lymphocyte count, proinflammatory mediators, and decreased level of interleukins as compared with the healthy population of females. The observed dynamic pretreatment and posttreatment shifts in serum inflammatory markers suggest involvement of adaptive immunity and angiogenic pathways, highlighting the potential role of inflammatory regulation in improving reproductive outcomes, including preparation for assisted reproductive technologies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4626 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4626/2331

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 29 1 9 EN Leila Ghasemi Hashtrodi Department of Pediatric Rheumatology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zahra Chavoshzadeh Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehrnaz Mesdaghi Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Narges Eslami Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Golnaz Eslamian Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehdi Alizadeh Children Growth Research Center, Research Institute for Prevention of Non-Communicable Diseases, Ghods Hospital, Qazvin University of Medical Sciences, Qazvin, Iran Leily Sokoty Department of Epidemiology, Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Alborz, Iran Shahrzad Fallah Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Asarehzadegan Dezfouli Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Heydarazad Zadeh Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Shabnam Hajiani Ghotbabadi Department of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran Hedieh Haji Khodavardi Khani Department of Immunology, Faculty of Medical Science, Shahed University, Tehran, Iran Nima Parvaneh Division of Allergy and Clinical Immunology, Department of Pediatrics, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Reza Sinaee Department of Pediatrics, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Azadeh Zeinab Mirzaee Pediatric Respiratory Disease Research Center (PRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nima Rezaei Research Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Samin Sharafian Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Reza Shiari Department of Pediatric Rheumatology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2025 04 04 2025 11 14 Combined immunodeficiencies (CIDs) represent a rare group of inherited immune disorders in which defects in T- and B-lymphocyte function lead to recurrent infections, immune dysregulation, and an increased tendency toward autoimmune and rheumatologic complications. A retrospective cross-sectional analysis was performed on 150 patients with CID, diagnosed according to the European Society for Immunodeficiencies (ESID) criteria and followed at the Children’s Medical Center and Mofid Children’s Hospital (Tehran, Iran) between 2009 and 2020. Clinical records, immunologic evaluations, and rheumatologic findings were reviewed, with particular attention to autoantibody detection and disease frequency. Among 150 patients, 42 (28%) exhibited rheumatologic manifestations, with a higher frequency in females. Undifferentiated rheumatoid arthritis, undifferentiated juvenile idiopathic arthritis, and Kawasaki disease were the predominant conditions. Although lower lymphocyte counts and immunoglobulin levels were observed among non-rheumatologic patients, the differences were not statistically significant. Impairments in T-cell–mediated immunity and antibody synthesis among individuals with CID hinder the recognition of autoantibody-associated rheumatologic disorders and delay diagnosis. Moreover, these conditions often present atypically in immunocompromised hosts; therefore, a vigilant clinical approach is essential for early identification and management. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4405 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4405/2332

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 30 1 11 Neda Ahmad Nejad Ahranjani Department of Biology, Faculty of Basic Sciences, Nabi Akram University, Tabriz, Iran Maryam Farghadan Human and Animal Cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran Mehrnoosh Pashaei Department of Research Development and Coordination, Deputy for Research and Technology, Ministry of Health and Medical Education, Tehran, Iran Sepideh Ashouri Movassagh Human and Animal Cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran Seyed Abolhassan Shahzadeh Fazeli Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 2025 12 04 2026 01 31 Gastric cancer is among the most prevalent malignancies worldwide, with a poor prognosis in advanced stages. Overexpression of human epidermal growth factor receptor 2 (HER2, also known as ERBB2) and heat shock protein 90 alpha (HSP90AA1, also known as HSP90α) has been associated with tumor progression. Anethum graveolens, a medicinal plant from the Apiaceae family, has demonstrated anticancer properties in previous studies. This study aimed to evaluate the effects of A graveolens methanolic extract on apoptosis and the expression of HER2, HSP90α, tumor protein p53 (TP53), and caspase-3 genes in the human gastric adenocarcinoma cell line (AGS). A methanolic extract of the aerial parts of A graveolens was prepared. Cytotoxicity was assessed in AGS and human gingival fibroblast (HUGU) cell lines using the -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Gene expression was measured by real-time PCR, and apoptosis was evaluated using Annexin V/propidium iodide (PI) staining followed by flow cytometry. The methanolic extract exhibited dose-dependent cytotoxicity, with a half-maximal inhibitory concentration (IC50) of 1280 μg/mL in AGS cells. Gene expression analysis revealed significant downregulation of HER2 and upregulation of HSP90α, TP53, and caspase-3 in treated AGS cells compared to controls. Apoptosis rates were significantly higher in treated AGS cells, confirming the proapoptotic effect of the extract. A graveolens exerts cytotoxic and proapoptotic effects in AGS cells and modulates key genes involved in gastric cancer progression. These findings suggest its potential as a natural therapeutic candidate for gastric cancer, warranting further preclinical and clinical investigations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4687 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4687/2333

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 30 1 17 Yonghui Zou Department of Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Yanqiu Wang Department of Anesthesia and Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Degao Liu Obstetrics and Gynecology Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China Changzhong Li Obstetrics and Gynecology Clinic, The People’s Hospital of Pingyi County, Linyi, Shandong, China Changling Li Obstetrics and Gynecology Clinic, The People's Hospital of Pingyi County, Linyi, Shandong, China 2025 08 07 2025 12 01 High risk human papillomavirus (HR-HPV) induced cervical intraepithelial neoplasia grade 1 (CIN1) is a low-grade lesion closely associated with persistent viral infection, and clinical management remains challenging. This study aimed to investigate clinical efficacy and immune response of recombinant human interferon α2b vaginal effervescent tablets in CIN1 caused by HR-HPV. In a retrospective study, 60 patients with HR-HPV and diagnosed with CIN1 from Shandong Provincial Hospital between December 2023 and December 2024 were divided into CT (n=30) and CR (n=30) groups, both groups were treated with conventional therapy, and recombinant human interferon α2b vaginal effervescent tablets were added to the CR group. The main assessment of both groups were inflammatory factor indicators, immune indicators, vaginal microenvironmental factors [hydrogen peroxide (H2O2) positivity, sialidase (SNA) positivity, leukocyte esterase (LE) positivity, N-acetylaminogalactosidase (NAG) positivity], HR-HPV conversion rate and clinical efficacy. Secondary outcomes included life quality scores, complication and adverse effect rates. After treatment, the indicators of both groups were significantly different from the pre-treatment. The changes in inflammatory indicators, immune indicators, SNA positivity rate, LE positivity rate, HR-HPV conversion rate, clinical efficacy, life quality, complications, and adverse reactions in the CR group were better than those in the CT group. No marked discrepancy was found in the comparison of H2O2 positivity rate and NAG positivity rate between both groups. Recombinant human interferon α2b vaginal effervescent tablets have significant therapeutic effects, as they alleviate inflammatory reactions, regulate immune indicators, and are worthy of clinical application and promotion. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4540 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4540/2334

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 06 1 13 EN Rahimeh Mohseni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Sara Soudi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Arezou Rahimi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Majid Sadeghizadeh Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Arezou Khosrojerdi Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2025 08 11 2025 12 28 Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to organ failure. This study examines the immunomodulatory effects of the M13 bacteriophage in a cecal ligation and puncture (CLP) mouse model of sepsis, comparing intravenous and intraperitoneal delivery routes. Key outcomes included cytokine responses, bacterial burden, organ injury, and survival. Sepsis was induced using the CLP model. M13 phages were verified by transmission electron microscopy and administered via IV or IP injection. Blood samples were collected at 24 hours, 72 hours, and day 5 for white blood cell, cytokine, and liver enzyme analysis. Bacterial burden was assessed by colony counts, liver injury by hematoxylin and eosin histology, and survival was monitored for 14 days. CLP induction caused marked increases in WBC counts, cytokines, C-reactive protein (CRP), bacterial load, and liver damage. Following phage treatment, inflammatory markers, bacterial burden, and tissue injury declined substantially. IV administration more effectively reduced systemic inflammation, whereas IP administration provided stronger protection of liver and kidney function and resulted in higher survival rates. M13 phage therapy demonstrates promising immunomodulatory and organ-protective effects in septic mice. The superior organ protection and survival benefits observed with IP delivery suggest potential translational value for targeted phage administration in sepsis management. Future studies should explore dose optimization, combination therapy, and mechanistic pathways to support clinical development. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4543 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4543/2335

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 06 1 10 EN Amirhossein Faghih Ojaroodi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran Neda Gholamzadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Khadijeh Pouya Department of Gynecology and Obstetrics, Faculty of Medicine, Tabriz Medical Sciences Islamic Azad University, Tabriz, Iran Sanaz Abbaspour-Aghdam Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Haleh Mikaeili Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Armin Sadeghi Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mehdi Nadiri Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2025 10 21 2026 01 31 Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung condition and a leading cause of morbidity and mortality worldwide. Despite well-established links to smoking, emerging evidence highlights the involvement of complex immune and epigenetic mechanisms in its pathogenesis. This study aimed to investigate the expression, secretion, and promoter methylation status of key pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with mild and severe COPD, compared with healthy individuals. PBMCs were isolated from 90 participants divided into three groups: severe COPD, mild COPD, and healthy controls. Quantitative polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and methylation-specific PCR were employed to evaluate gene expression, protein secretion, and promoter methylation of inflammatory cytokines. Patients with COPD exhibited significant upregulation of pro-inflammatory cytokines (Interleukin1β (IL-1β), IL-6, IL-18, IFN-γ, and TNF-α) at both transcript and protein levels, with more pronounced alterations in the severe group. Conversely, anti-inflammatory mediators (IL-10 and TGF-β) were significantly downregulated. Promoter methylation analysis revealed hypomethylation in pro-inflammatory cytokine genes and hypermethylation in anti-inflammatory ones, correlating with disease severity. The findings demonstrate that COPD progression is associated with a shift toward a hyper-inflammatory, hypo-regulatory immune phenotype sustained by epigenetic modifications. These results support the potential for integrating cytokine-methylation signatures into clinical staging and for targeting epigenetic and immune pathways in future therapeutic strategies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4638 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4638/2336

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 17 1 13 Nima Jadidian Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Ali Hazrati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Arsalan yazdchi Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran Hamed Valizadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Reza Taban-Sadeghi Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Haleh Mikaeili Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran 2 Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2025 10 21 2026 01 25 The airflow limitation is one of the characteristics of chronic obstructive pulmonary disease (COPD), which is not entirely reversible. It seems that factors such as inflammation, hypoxia, and remodeling of pulmonary vessels can increase pulmonary hypertension (PH). This increase in pulmonary arterial hypertension leads to aggravation of disease complications. Considering the role of immune cells in causing pathological inflammation in the pathogenesis of COPD, it seems that Th17/Treg axis imbalance can be one of the main reasons for the difference in life expectancy in patients with COPD with and without PH. By measuring and comparing some inflammatory biomarkers in patients with COPD with and without PH, this study tries to introduce these biomarkers to predict the occurrence or nonoccurrence of this complication. This study aims to compare the ratio and activity of Th17 to Treg in patients with COPD with high (20 patients) and normal (20 patients) pulmonary arterial pressure. Five milliliters of blood containing anticoagulant were obtained to isolate peripheral blood mononuclear cells (PBMCs). Then, the ratio of Th17 to Treg, their number, and their activity were evaluated by ELISA, real-time polymerase chain reaction (PCR), and flow cytometry. Our results show that the amount of inflammatory factors and the population of Th17 cells in patients with COPD with PH is associated with a significant increase in PH compared to patients with COPD without PH, which leads to damage caused by pathological inflammation to the lung tissue and a decrease in the overall survival of the patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4639 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4639/2338

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 9 Vahid Ghobadi Dana Department of Photodynamic, Medical Laser Research Center, Yara Institute, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran Seyed Saeed Hashemi Nazari Department of Epidemiology, Prevention of Cardiovascular Disease Research Center, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran Ali Pourvali Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Masoud Habibi Department of Photohealing and Regeneration, Medical Laser Research Center, Yara Institute, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran Mohsen Fateh Department of Lifestyle Medicine, Medical Laser Research Center, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran Maedeh Arabian Cardiogenic Research Center, Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran Farhad Seif Department of Photodynamic, Medical Laser Research Center, Yara Institute, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran Ahmad Vosughi Motlagh Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran 2025 07 22 2025 12 01 Allergic rhinitis (AR) is a common inflammatory condition characterized by symptoms such as nasal congestion, rhinorrhea, sneezing, and nasal itching, which significantly impact quality of life. Management includes allergen avoidance, pharmacological therapy, and, in severe cases, immunotherapy. Ipratropium bromide, an anticholinergic agent, is primarily used for managing rhinorrhea by inhibiting acetylcholine-mediated secretion in the nasal mucosa. To evaluate the effects and side effects of ipratropium bromide nasal spray in combination with low-dose budesonide in patients with allergic rhinitis, a double-blind, randomized, placebo-controlled trial was conducted with 126 patients diagnosed with AR. Participants were randomly assigned to receive one of three treatments: Ipranasal 42 μg + budesonide, Ipranasal 21 μg + budesonide, or placebo + budesonide, over a two-week period. Symptom severity was assessed using the ARIA questionnaire and visual analog scale (VAS) for nasal symptoms at baseline and two weeks after the intervention. Significant reductions in rhinorrhea were observed in the Ipranasal groups compared to the placebo group. Mild side effects, including nasal and oral dryness, were transient and non-significant. There were no major differences between the 42 μg and 21 μg groups in terms of efficacy or side effects. Ipratropium bromide nasal spray effectively reduces rhinorrhea in AR patients, with good tolerability. However, it also had moderate effects on nasal congestion. Combination therapy may enhance symptom control, but further studies are needed to assess long-term efficacy and safety. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4530 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4530/2340

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 14 Milad Karimi Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Reza Falak Breast Cancer Research Center, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mahdi Fasihi-Ramandi Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ramezan-Ali Taheri Nanobiotechnology Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 12 13 2026 02 01 Cervical cancer is the fourth most prevalent malignancy among women globally. Zinc oxide nanoparticles (ZnO-NPs) possess significant potential in cancer therapy due to their unique physicochemical properties, biocompatibility, and apoptosis-inducing abilities. While ZnO-NPs have been examined in HeLa cells and peripheral blood mononuclear cells (PBMCs) individually, their immunological and angiogenesis-related effects in immune-tumor co-culture systems was insufficiently investigated. This study assessed the apoptotic, anti-angiogenic, and cytokine-modulating effects of ZnO-NPs in a HeLa/PBMC co-culture model. HeLa cells were co-cultured with PBMCs and treated with ZnO-NPs under different groups. Cytotoxicity was evaluated using MTT assay, apoptosis was analyzed by flow cytometry, and gene expression levels were measured using real-time PCR. ZnO-NPs significantly reduced HeLa cells viability with a half maximal inhibitory concentration (IC50) of 7 µg/mL, while PBMCs showed more resistance (IC50=40 µg/mL). In the HeLa/PBMC/ZnO co-culture group, gene expression analysis in PBMCs revealed significant upregulation of IL1B, TNF, IFNG, and TGFB1 compared with the HeLa/PBMC group, while IL2 and IL4 expression levels showed no significant changes. VEGFA expression in HeLa cells was reduced in all treated groups, with the greatest decrease in the HeLa/PBMC/ZnO group. Co-culture with PBMCs and ZnO-NP treatment significantly promoted apoptosis in HeLa cells. In conclusion, ZnO-NPs induce cytotoxic and anti-angiogenic effects on HeLa cells, particularly within a PBMC co-culture setting, highlighting the contribution of immune–tumor interactions to ZnO-NP–mediated anti-cancer responses; however, more investigations at the protein and functional levels are necessary to validate these effects. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4699 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4699/2343

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 15 Guifang Jiang Clinical Laboratory, Huzhou Wuxing District People’s Hospital, Huzhou Wuxing District Maternal and Child Health Hospital, Huzhou, China Junping Pan Laboratory, Huzhou Wuxing District Center for Disease Prevention and Control (Wuxing District Health Supervision Institute), Huzhou, China 2026 01 01 2026 02 08 Progression from chronic hepatitis B (CHB) to cirrhosis is closely associated with immune dysregulation and altered cytokine signaling, yet effective noninvasive immune biomarkers remain limited. This study aimed to develop a peripheral blood mononuclear cell (PBMC)-based cytokine gene signature for predicting HBV-related cirrhosis. The GSE114783 microarray dataset was analyzed to identify differentially expressed genes between CHB and cirrhosis. Immune-related candidate genes were selected by integrating curated immune resources and the Kyoto Encyclopedia of Genes and Genomes cytokine-cytokine receptor interaction pathway. Least absolute shrinkage and selection operator regression and multivariable logistic regression were used to construct the predictive model. Receiver operating characteristic analysis, leave-one-out cross-validation, and nomogram development were performed to evaluate model performance and support clinical translation. Differential expression analysis identified 3169 genes distinguishing cirrhosis from CHB, from which 86 immune/cytokine-related genes were prioritized. LASSO selected a parsimonious 4-gene signature-CXCR1, IL11RA, IL13RA2, and CD19-capturing key immune axes relevant to chronic inflammation and fibrogenesis (chemokine receptor signaling, IL-11/IL-13 receptor pathways, and B-cell–associated immunity). The resulting model achieved an area under the curve (AUC) of 0.935 (95% CI, 0.882-0.988); at an optimal cutoff of 0.832, sensitivity was 88.6% and specificity 84.3%. LOOCV supported robust performance, and the nomogram demonstrated good agreement between predicted and observed risk. A PBMC-based immune cytokine-receptor gene signature (CXCR1/IL11RA/IL13RA2/CD19) provides a noninvasive tool for immunologically informed risk stratification of HBV-related cirrhosis and may support immune monitoring and early intervention strategies. Prospective, multicohort validation and mechanistic studies are warranted. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4729 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4729/2344

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 9 Qiang Zhou Department of Emergency, Ningbo Yinzhou No.2 Hospital, Ningbo, China Jun Lin Department of Emergency, Ningbo Yinzhou No.2 Hospital, Ningbo, China 2025 12 24 2026 01 28 Continuous blood purification (CBP) has been widely employed in adult sepsis management. However, given the distinct aetiology and host responses in paediatric sepsis compared to adults, the application of CBP in children remains under-researched in high-quality systematic studies, particularly regarding its efficacy in clearing inflammatory cytokines. This meta-analysis aims to evaluate the therapeutic efficacy of CBP in paediatric sepsis patients and its impact on inflammatory cytokines. This study systematically analysed randomized controlled trials and prospective cohort studies of CBP in paediatric sepsis from January 1990 to October 2025. Studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science. Outcomes included inflammatory markers and prognostic markers. This meta-analysis included 6 studies. Pooled results demonstrated that CBP reduced 28-day mortality (OR = 0.57, 95% CI: 0.30 to 1.07), PICU length of stay (OR = −0.06, 95% CI: −1.55 to 1.43), IL-6 (OR = 0.83, 95% CI: 0.14 to 1.53), CRP (OR = 1.26, 95% CI: −16.51 to 19.03), and TNF-α (OR = 1.66, 95% CI: −0.39 to 3.77). CBP reduced the level of inflammatory markers and improved prognosis, which may provide evidence for the use of CBP in paediatric sepsis patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4718 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4718/2345

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 7 Yabin Chen Department of Pediatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China Hua Xu Department of Pediatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China Xunchao Ji Department of Pediatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China Juan Xiao Nursing and Rehabilitation College, Fuzhou Medical College, Fuzhou, Jiangxi, China 2025 12 08 2026 02 01 To investigate the association between single nucleotide polymorphism (SNP) of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) +49A/G locus and the risk of asthma in children by meta-analysis. Six databases were searched for records on the association between CTLA-4 +49A/G locus polymorphism and pediatric asthma. The retrieval time was from the establishment of each database to July 2024. Stata 15.0 software was applied, with the pooled OR and 95% CI calculated. Five genetic models (G/A, GA+AA/AA, G/GA+AA, GG/AA, and GA/AA) were analyzed. Nine studies were included, covering 2133 Cases and 1572 controls. The combined results exhibited that the differences were all statistically significant under the allelic (OR, 0.53; 95% CI, 0.35-0.79), dominant (OR, 0.41; 95% CI, 0.24-0.71), recessive(OR, 0.60; 95% CI, 0.41-0.89), homozygous (OR, 0.38; 95% CI, 0.22-0.68) and heterozygous (OR, 0.52; 95% CI, 0.33-0.80) models. The meta-analysis indicates that CTLA-4 +49A/G SNP is related to susceptibility to pediatric asthma, and allele G and genotype GG+GA, GG, and GA correlated with a decreased risk of asthma. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4692 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4692/2346

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 19 1 18 EN Shenglong Wu Department of Radiology, Hainan Women and Children’s Medical Center Bing Zhu Department of Radiology, Hainan Women and Children’s Medical Center, Changbin Road, Xiuying District, Haikou, Hainan 570000, China 2026 02 02 2026 03 12 Cerebral small vessel disease (CSVD) is increasingly recognized as a chronic immune-mediated microvascular disorder, in which sustained systemic inflammation contributes to endothelial dysfunction, blood–brain barrier (BBB) disruption, and progressive brain injury. Pro-inflammatory cytokines and acute-phase reactants, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP), have been implicated in cerebrovascular immune dysregulation; however, their specific associations with magnetic resonance imaging (MRI)–defined CSVD phenotypes remain incompletely understood. A systematic literature search of PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang databases was conducted from inception to December 2025. Observational studies reporting independent associations between circulating inflammatory markers and MRI features of CSVD—including white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB)—were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models based on heterogeneity. Eighteen eligible studies were included in the meta-analysis. Elevated IL-6 levels were significantly associated with increased risks of LI (OR = 1.53, 95% CI: 1.11–2.11) and CMB (OR = 1.28, 95% CI: 1.06–1.55), reflecting cytokine-driven immune activation and BBB vulnerability. Increased hs-CRP levels were significantly correlated with WMH (OR = 2.19, 95% CI: 1.18–4.07), LI (OR = 1.97, 95% CI: 1.21–3.20), and CMB (OR = 1.67, 95% CI: 1.37–2.04), consistent with chronic low-grade systemic inflammation and endothelial injury. In contrast, conventional CRP showed no significant association with CSVD imaging markers. Elevated fibrinogen levels were specifically associated with WMH (OR = 1.48, 95% CI: 1.21–1.80), suggesting an interaction between inflammatory–coagulative pathways and microvascular white matter damage. This meta-analysis demonstrates that systemic inflammatory cytokines and acute-phase proteins are closely linked to immune-mediated microvascular injury underlying MRI-defined CSVD phenotypes. IL-6 and hs-CRP, in particular, may serve as accessible immunological biomarkers reflecting chronic vascular inflammation and BBB dysfunction in CSVD. These findings support an immunopathological framework for CSVD and provide evidence for incorporating inflammatory markers into immune-focused risk stratification and early intervention strategies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4576 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4576/2347

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 24 1 15 DongDong Feng Department of Pediatrics, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, Guangxi Zhuang Autonomous Region, China Chao Chen Pediatric Intensive Care Unit (PICU), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China HuiMin Huang Pediatric Intensive Care Unit (PICU), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China XueQiong Huang Pediatric Intensive Care Unit (PICU), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 2025 07 04 2025 10 07 Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection in immunocompromised children, often causing acute fulminant pneumonia with respiratory failure. The prognosis of PJP in human immunodeficiency virus (HIV)-negative children with acute respiratory distress syndrome (ARDS) remains unclear. This retrospective review (2015–2021) included 20 HIV-negative children with ARDS and PJP. Among them, 17 had hematological malignancies or solid tumors, and 3 had renal disease; 15 survived, 5 did not. Both groups had very low CD4+ T cell counts (<0.2×10⁹/L), severe ARDS (partial pressure of oxygen in arterial blood / fraction of inspired oxygen [PaO₂/FiO₂] ratio <150), and elevated lactate dehydrogenase (LDH) and (1,3)-β-D-glucan (BDG) levels. In non-survivors, anti-PJP therapy was initiated approximately 7 days later than in survivors. Single-cell sequencing revealed CD4+/CD8+ T cell ratios of 0.16 (survivors) vs 2.13 (non-survivors), with a higher ratio of regulatory T cells (Tregs) to CD4⁺ T cells in non-survivors (33% vs. 10.6%). Non-survivors showed enrichment of neutrophil degranulation and activation pathways and expressed more proapoptotic and proinflammatory signals (e.g., FAS_FASLG, interferon-γ). Early treatment initiation is critical. Prolonged CD8+ T cell deficiency, high Treg expression with proapoptotic genes, and excessive inflammation may predict poor prognosis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4506 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4506/2348

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 30 1 15 Jixiang Liu Department of Health Insurance Affairs, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China Shan Liu Department of Clinical Laboratory, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China Jinghang Cong Department of Clinical Laboratory, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China Xuesong Zhao Department of Clinical Laboratory, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China Liwei Zhang Department of Gastroenterology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China Wei Li Department of Clinical Laboratory, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China 2025 10 28 2026 01 27 Colon cancer, a leading cause of death, demands early detection. We evaluate serum S100 calcium-binding protein A12 (S100A12) and diamine oxidase (DAO) effects on gut dysbiosis/immunity and their combined diagnostic value. This retrospective study included 105 colon cancer patients (study group), 90 benign lesions, and 105 matched healthy controls. Serum S100A12 and DAO were measured by ELISA (enzyme-linked immunosorbent assay). Gut flora (Escherichia coli, Enterococcus faecalis, Bifidobacterium, Lactobacillus) were cultured; T cell subsets (CD4+, CD8+, Treg) by flow cytometry. Patients were stratified by median levels into high/low groups. Correlations and diagnostic efficacy were assessed using Pearson test and ROC (receiver operating characteristic) analysis. Baseline data were comparable among three groups. Fecal flora (E. coli, E. faecalis, Bifidobacterium, Lactobacillus) and T cells (CD4+, CD8+, regulatory T cells) differed significantly. Serum S100A12 and DAO were elevated in colon cancer versus benign/control groups. High/low subgroups showed disparities in flora and T cells. S100A12 and DAO positively correlated with E. coli/E. faecalis, CD8+ T, and Treg, but negatively with Bifidobacterium, Lactobacillus, and CD4+ T. The cancer group had reduced CD4+ and CD4+/CD8+ ratio, and elevated CD8+ and Treg. Combined S100A12+DAO detection outperformed single markers. Elevated serum S100A12 and DAO in colon cancer are associated with gut microbiota dysbiosis and immune dysregulation. Their combination shows promise as a potential biomarker for early diagnosis and disease evaluation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4643 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4643/2350

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 06 02 1 17 EN Mahdi Behi Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Babak Gholamine Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohammad Reza Masjedi Tobacco Control Research Center (TCRC), Iranian Anti-Tobacco Association, Tehran, Iran AND Department of Pulmonary Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Alireza Eslaminejad Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Esmaeil Idani Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohsen Sadeghi Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Akram Qanavati Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Sayed Mehran Marashian Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Esmaeil Mortaz Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands Atefeh Abedini Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mihan Pourabdollah Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Bita Pakshad Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Saeid Mahmoodian Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2025 09 01 2026 02 07 Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of morbidity, mortality, and healthcare burden. While standard bronchodilator therapy alleviates airway obstruction, its efficacy is often limited. This study evaluated nebulized furosemide, which has bronchodilatory and anti-inflammatory effects, as an adjunct to salbutamol–ipratropium in hospitalized COPD patients. Ninety‑two patients with exacerbated COPD were randomly assigned to two equal groups (46 each). The intervention group received nebulized salbutamol–ipratropium plus furosemide (20 mg), and the control group received salbutamol–ipratropium, both every 8 hours for 10 minutes over 5 consecutive days. Demographic and clinical variables, pulmonary function indices (FEV1, FVC, FEV1/FVC), clinical outcomes (COPD Assessment Test (CAT), Modified Medical Research Council (mMRC)scores, and quality of life by St. George’s Respiratory Questionnaire (SGRQ)), arterial blood gases, and inflammatory biomarkers (TNF-α, IL-6, IL-8, CRP, ESR, neutrophil %, WBC) were measured before and after treatment. Demographic characteristics and baseline indices did not differ significantly between the groups. Dyspnea and respiratory symptoms (mMRC and CAT scores) decreased significantly, while quality of life, improved markedly in the intervention group compared to the control group. Pulmonary function also showed significant enhancement, with the FEV₁/FVC ratio increasing. Arterial blood gas analysis showed higher PaO₂ and lower PaCO₂ in the intervention group. IL-6 and IL-8 decreased significantly, and no adverse events were reported. Nebulized furosemide enhances standard therapy in COPD exacerbations, improving lung function, relieving symptoms, and reducing systemic inflammation. Its safety, accessibility, and low cost make it a promising adjunct treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4569 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4569/2353

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 06 02 1 15 Lianxing Zhang Department of Digestive Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China Xia Han Department of Digestive Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China Yue Wang Department of Digestive Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China Yanrong Li Department of Digestive Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China Jia Wang Department of Digestive Oncology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China 2025 12 26 2026 01 28 While immune checkpoint inhibitors (ICIs) are a key treatment for advanced gastric cancer (AGC), the prognostic significance of their associated immune-related adverse events (irAEs) remains unclear. This real-world study aims to evaluate irAE incidence and impact on clinical outcomes. This retrospective study consecutively enrolled 156 patients with AGC who received ICI therapy and completed follow-up between January 2021 and June 2023. Baseline characteristics, treatment regimens, irAE occurrence, and survival data were collected. The prognostic impact of irAEs was assessed by objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). A total of 156 patients were included, of whom 76 (48.72%) developed irAEs. The most  common types were endocrine, cutaneous, and gastrointestinal toxicities, mostly of grades 1-2. Multivariate logistic regression analysis identified age≥70 years (OR=2.615), BMI ≥ 25 kg/m² (OR=5.791), prior chemotherapy (OR=4.954), prior targeted therapy (OR=5.532), ICI combined with chemotherapy (OR=5.456), ICI combined with targeted therapy (OR=2.850), and a history of smoking (OR=3.224) as independent predictors of irAEs. Compared with the non-irAEs group, the irAEs group showed superior clinical efficacy, with a significantly higher ORR (38.16% vs. 20.00%) and DCR (80.26% vs. 66.25%). Kaplan-Meier survival analysis revealed a significant association between the occurrence of irAEs and prolonged survival, with the irAEs group showing superior median PFS (8.0 vs. 5.0 months) and OS (15.0 vs. 10.0 months) compared to the non-irAEs group. For AGC patients receiving ICI therapy, the development of irAEs correlates significantly with improved survival, serving as a potential biomarker of clinical benefit. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4722 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4722/2354

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 11 1 14 Li Dong Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China Yue Zhao Clinical Laboratory, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China Yuqi Sun Clinical Laboratory, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China Fuxin Cui Clinical Laboratory, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China 2025 06 26 2025 11 24 Breast cancer is a leading malignancy in women. Understanding its clinicopathological traits and microsatellite status is vital for prognosis and treatment planning. This study explored the links between preoperative pan-immune-inflammation value (PIV) and hemoglobin, albumin, lymphocyte, and platelet (HALP) score with breast cancer’s pathological features and microsatellite status and assessed their predictive power for the latter. This retrospective study analyzed data from 260 breast cancer patients who had surgery between 2022 and 2025. Researchers not involved in the patients’ treatment collected and analyzed the data. HALP and PIV were calculated from preoperative blood tests. Patients were grouped based on the median values of these scores. Associations between the scores and clinicopathological characteristics were examined. Patients were also divided into microsatellite stable (MSS) and microsatellite instability-high (MSI-H) groups, and differences in HALP and PIV between these groups were compared. Receiver operating characteristic curves were used to evaluate the predictive accuracy of HALP and PIV for microsatellite status. High PIV was linked to younger age and lower ER positivity. High HALP correlated with older age, a higher proportion of clinical stage I patients, and lower HER2 positivity. MSS patients had lower PIV and higher HALP than MSI-H patients. PIV and HALP showed significant correlations with microsatellite status. Both indicators had high AUC values (PIV: 0.867; HALP: 0.879), with 100% sensitivity, indicating strong predictive capabilities. Preoperative PIV and HALP are closely tied to breast cancer’s pathological features and microsatellite status. They offer high predictive value for microsatellite status, aiding in breast cancer diagnosis and treatment decisions.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4497 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4497/2319

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 14 Xiaomeng Guan Department of Anesthesiology, Baoding Second Central Hospital, Baoding, Hebei, China Huizhen He Department of Anesthesiology, Baoding Second Central Hospital, Baoding, Hebei, China 2025 10 07 2025 12 28 Background: Surgical stress in pediatric adenotonsillectomy can trigger marked immune and inflammatory disturbances. Esketamine, beyond its anesthetic role, has been reported to exhibit immunomodulatory and anti-inflammatory properties. However, its dose-dependent impact on perioperative immune homeostasis in children remains unclear.   Surgical stress in pediatric adenotonsillectomy can trigger marked immune and inflammatory disturbances. Esketamine, beyond its anesthetic role, has been reported to exhibit immunomodulatory and anti-inflammatory properties. However, its dose-dependent impact on perioperative immune homeostasis in children remains unclear. This study aimed to investigate the impact of varying doses of esketamine on perioperative inflammatory cytokines, immune cell balance, and humoral immune markers in pediatric patients undergoing adenotonsillectomy. Ninety pediatric patients (3–10 years) were retrospectively assigned into three groups based on the esketamine dose they received: low-dose (0.25 mg/kg), medium-dose (0.5 mg/kg), or high-dose (1 mg/kg) esketamine. Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) were measured to assess systemic inflammation, while CD4+/CD8+ ratios, immunoglobulin (Ig) A, and IgG were evaluated as immune function indices at baseline, 1 hour, and 24 hours postoperatively. Hemodynamic parameters and clinical recovery indices were also recorded. Compared with the low-dose and high-dose groups, the 0.5 mg/kg esketamine group showed significantly attenuated elevations in IL-6 and CRP, a faster normalization of the CD4+/CD8+ ratio, and preservation of IgA levels within near-normal range. These immunological benefits coincided with improved postoperative recovery and fewer adverse events. No significant differences were observed in IgG levels among groups. This study identifies 0.5 mg/kg as a potential immunoprotective threshold for esketamine, effectively mitigating perioperative immune suppression and excessive inflammation in children undergoing adenotonsillectomy, an insight beyond its known anesthetic properties. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4612 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4612/2326

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 31 1 7 Mehrshad Ebrahim pour Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran Abdullah Moridikia Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Ebrahim Salimi-Sabour Department of Pharmacognosy and Traditional Pharmacy, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 12 26 2026 02 06 Sepsis-induced immunothrombosis is driven in part by dysregulated neutrophil extracellular traps (NETs), yet existing therapies fail to adequately address the oxidative checkpoints that initiate this cascade. This mechanistic Perspective proposes a paradigm shift toward dual-functional inorganic nanomedicine aimed at modulating both inflammation and coagulation. We discuss emerging evidence supporting a “prevention-plus-clearance” strategy employing PEGylated cerium oxide nanoparticles (nanoceria) surface-grafted with DNase I. The inorganic core functions as a prolonged superoxide dismutase–like redox buffer through the regenerative Ce³⁺/Ce⁴⁺ cycle, thereby attenuating reactive oxygen species (ROS)-dominant NETosis pathways rather than universally blocking NET formation. In parallel, the surface-immobilized DNase I facilitates enzymatic degradation of extracellular chromatin scaffolds. We hypothesize that this bio-inorganic combination may address the biphasic nature of sepsis pathogenesis by limiting NET initiation while promoting microvascular de-obstruction. Finally, we outline a translational roadmap required to validate this “circuit-breaker” strategy in vivo, positioning the cerium–NETosis axis as a promising frontier in the management of sepsis-associated coagulopathy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4724 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4724/2351

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 17 1 15 Ensiye Torki Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Nahid Eskandari Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Kiana Sami Aix-Marseille University, Marseille, France Arezou Gharezadeh Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mark Sullman Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus AND Department of Social Sciences, University of Nicosia, Nicosia, Cyprus Shakiba Soltani Shiraz Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Hamed Fouladseresht Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran AND Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran 2025 09 10 2026 02 01 Long COVID syndrome (LCS) is characterized by persistent multi-system manifestations with an unclear underlying pathophysiology. Identifying the genetic and immunological factors associated with LCS is essential for improved risk stratification and clinical management. This study investigated whether incorporating HLA-DRB1* and HLA-DQB1* genotyping data could enhance the predictive value of laboratory parameters for identifying individuals at higher risk of developing LCS. Demographic characteristics and relevant clinical history data were extracted from the medical records of 88 individuals diagnosed with LCS (LCS+) and 96 individuals without LCS (LCS−). Serum levels of anti-receptor binding domain IgG (anti-RBD IgG), anti-β2-glycoprotein I IgG (anti-β2GPI IgG), and C-reactive protein (CRP) were measured. Low-resolution genotyping was performed to identify HLA-DRB1* and HLA-DQB1* alleles. Logistic regression analysis was employed to examine the associations between HLA alleles and LCS status. Subsequently, mediation analysis was conducted to explore the potential mechanistic roles of anti-RBD IgG, CRP, and anti-β2GPI IgG in these observed relationships. The LCS+ group exhibited a significantly higher frequency of the HLA-DRB1*01 allele and a lower frequency of the HLA-DRB1*11 than the LCS− cohort. Serum levels of both CRP and anti-β2GPI IgG were substantially higher in the LCS+ cohort, whereas anti-RBD IgG levels were significantly lower. After adjusting for key variables, HLA-DRB1*01 and HLA-DRB1*11 remained significantly associated with LCS. Mediation analysis suggested that these HLA associations might be partially mediated by CRP, anti-RBD IgG, and anti-β2GPI IgG levels. Our findings indicate that the combination of HLA-DRB1*01 and HLA-DRB1*11 allele screening with serological profiling (anti-RBD IgG, CRP, and anti-β2GPI IgG) may contribute to refining predictive models of LCS susceptibility, though clinical utility requires validation in larger, independent cohorts. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4581 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4581/2339