Iranian Journal of Allergy, Asthma and Immunology

Immunological Mechanisms of the Gut–brain–cardiovascular Axis in Coronary Heart Disease with Comorbid Anxiety and Depression

2026-08-16T11:07:12+0430

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.

Immune-related Circulating Biomarkers in Intracerebral Hemorrhage: Implications for Nursing Management and Prognostic Assessment

2026-08-16T11:07:13+0430

Intracerebral hemorrhage (ICH) remains one of the most severe stroke subtypes and requires continuous risk assessment across the acute, subacute, and rehabilitation-transition phases. This review summarizes established and emerging immune-related circulating biomarkers and discusses their relevance to nursing management and prognostic assessment. Markers with the highest current clinical readiness include peripheral blood cell counts and derived ratios, C-reactive protein (CRP), and procalcitonin (PCT), whereas cytokines, chemokines, broader immunometabolic mediators, and neuroinjury-inflammation cross-over markers remain mainly investigational. On the basis of the revised synthesis, we propose a stage-specific monitoring framework that emphasizes sampling at admission, approximately 24 hours, approximately 72 hours, and at clinically triggered reassessment points, together with interpretation of trajectories rather than isolated values. We further outline practice-oriented nursing scenarios in which biomarker trends may support escalation of neurologic observation, infection surveillance, airway care, glucose and nutrition management, structured handoff communication, and multidisciplinary coordination. Current evidence suggests that routinely available biomarkers may add value as adjunctive monitoring tools, but the literature remains limited by observational designs, heterogeneous assay platforms, inconsistent sampling windows, variable endpoints, incomplete confounder control, and uncertain action thresholds. At present, biomarkers should complement rather than replace imaging, neurological examination, and bedside nursing assessment. Future prospective studies should prioritize standardized sampling, trajectory-based analyses, integration into nursing workflows, and clinically interpretable multimodal models.

Efficacy of Blood Purification in Paediatric Sepsis and Its Effects on Inflammatory Cytokines: A Systematic Review and Meta-analysis

2026-08-16T11:07:12+0430

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.

Association between Serum Innate Immunity-related Inflammatory Markers and MRI Features of Cerebral Small Vessel Disease: A Systematic Review and Meta-analysis

2026-08-16T11:07:12+0430

Cerebral small vessel disease (CSVD) is a microvascular disorder associated with endothelial dysfunction, blood–brain barrier disruption, and chronic immune inflammation. However, the relationships between circulating inflammatory markers and magnetic resonance imaging (MRI) features of CSVD remain unclear.
A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases was conducted from inception to December 2025. Observational studies evaluating associations between serum inflammatory markers and MRI-defined CSVD features, including white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB), were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models.
Eighteen studies were included. Elevated interleukin-6 (IL-6) levels were significantly associated with LI (OR=1.53, 95% CI: 1.11–2.11) and CMB (OR=1.28, 95% CI: 1.06–1.55). Increased high-sensitivity C-reactive protein (hs-CRP) levels were significantly associated 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). Elevated fibrinogen (FIB) levels were significantly associated with WMH (OR=1.48, 95% CI: 1.21–1.80). In contrast, conventional C-reactive protein showed no significant association with CSVD imaging markers.
This meta-analysis demonstrates that elevated IL-6, hs-CRP, and FIB levels are associated with MRI features of CSVD, supporting the involvement of innate immune inflammation in CSVD pathophysiology. These markers may reflect chronic cerebral microvascular injury and endothelial dysfunction. However, causal relationships cannot be established, and further prospective studies are required.

Immunity as Cornerstone of Non-alcoholic Fatty Liver Disease: The Contribution of Innate and Adaptive Immune Mechanisms in the Pathogenesis of the Metabolic Syndrome-related Steatohepatitis

2026-08-16T11:07:13+0430

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 [T_H17], 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.

Preoperative PIV and HALP: Correlation with Breast Cancer Pathology and Predictive Value for Microsatellite Status

2026-08-16T11:07:13+0430

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.

Effects of Propofol–remifentanil on Apoptotic Molecules, Plasma CXCL10, and CXCL13 in Pancreatic Cancer Patients

2026-08-16T11:07:13+0430

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.

Phenotyping of TH9 Cells in Cytomegalovirus-reactivated Kidney Transplant Recipients

2026-08-16T11:07:13+0430

Human cytomegalovirus (HCMV) is a frequent complication in kidney transplant recipients (KTRs), often impacting immune regulation. T_H9 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 T_H9 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 T_H9 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 T_H9 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⁺ T_H9 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 T_H9 cells and their signature cytokine IL-9 in the antiviral immune response in KTRs. While T_H9 cells may contribute to HCMV-related immune modulation, further research is needed to fully elucidate their protective mechanisms against viral infections.

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Peripheral Blood Immunogenomic Cytokine-receptor Signature (CXCR1, IL11RA, IL13RA2, CD19) Predicts HBV-related Cirrhosis: Public PBMC Transcriptome Mining and Nomogram Development

2026-08-16T11:07:13+0430

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.

The Role of Hyperthermia in Enhancing Anti-tumor Efficacy of Pemetrexed and Altering hsa-MiR-548c-3p Expression Profile in A549 Cell Line (Human Lung Cancer)

2026-08-16T11:07:13+0430

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.

Association between CTLA4 +49A/G Polymorphism and Childhood Asthma Susceptibility: A Meta-analysis

2026-08-16T11:07:13+0430

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.

Delayed Severe Presentation of Chronic Granulomatous Disease in Adulthood: A Case Report

2026-08-16T11:07:12+0430

Chronic granulomatous disease (CGD) is the most common inherited phagocytic Disorder with an increased susceptibility to recurrent infections and inflammatory manifestations due to a defect in any of the 5 NADPH oxidase subunits. Although CGD may manifest at different ages based on the defects of NADPH oxidase proteins, it is usually diagnosed in childhood with an overall median age of 2.7 to 3 years at the onset.
Infections and inflammatory manifestations are known to be two major clinical presentations of CGD, with the infections occurring much earlier in life than the inflammatory manifestations. Despite the patients’ clinical history and their noticeable manifestations, sometimes the diagnosis is delayed until adulthood, which could be attributed to physicians’ low awareness of the disease. Another reason for such delayed diagnosis could be the fact that some CGD mutations may remain asymptomatic up to a certain age.
The current study is a report of a healthy woman without any history of recurrent infections or inflammation until she was forty. In her early forties, she contracted a mycobacterial infection that was unresponsive to treatment, and was then diagnosed with abnormal reactive oxygen species released by neutrophils, suggesting a case of CGD.
This suggests that primary immunodeficiencies are not solely childhood disorders and should be considered in all refractory or therapy resistant conditions, even in adults.

Pharmaceutical Care for Adrenal Crisis Induced by Sintilimab Immunotherapy

2026-08-16T11:07:12+0430

No abstract

Serum Inflammatory Marker Changes in Women with Uterine Fibroids before and after Treatment

2026-08-16T11:07:12+0430

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.