Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 504 509 EN Marco Yamazaki-Nakashimada Department of Pediatric Clinical Immunology, Instituto Nacional de Pediatria. Mexico City, Mexico Patricia Herrera-Mora Department of Pediatric Neurology, Instituto Nacional de Pediatria. Mexico City, Mexico Alfonso Mahrx-Bracho Department of Pediatric Neurosurgery, Instituto Nacional de Pediatria. Mexico City, Mexico Gabriela López-Herrera Immunodeficiencies Research Unit, Instituto Nacional de Pediatria. Mexico City, Mexico Juan Bustamante-Ogando Immunodeficiencies Research Unit, Instituto Nacional de Pediatria. Mexico City, Mexico Selma Scheffler-Mendoza Department of Pediatric Clinical Immunology, Instituto Nacional de Pediatria. Mexico City, Mexico 2022 02 14 2023 05 17 Most patients with X-linked agammaglobulinemia are susceptible to infections, while some cases also suffer from inflammatory or autoimmune complications. We describe a patient with progressive encephalitis who improved after the use of immunomodulatory treatment with corticosteroids, fluoxetine, and nitazoxanide. In most of the cases the evolution of the progressive encephalitis is complicated and catastrophic. Based on our experience and the review of the literature, we propose the use of this combined treatment to control this devastating complication. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3457 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3457/1984

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 413 419 EN Mohsen Jafari Division of Infectious Diseases, Department of Pediatrics, Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran Masoomeh Sobhani Department of Pediatrics, Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran Kambiz Eftekhari Division of Gastroenterology, Department of Pediatrics, Pediatric Gastroenterology and Hepatology Research Center, Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran Armen Malekiantaghi Division of Gastroenterology, Department of Pediatrics, Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran Mohammad Gharagozlou Department of Allergy and Clinical Immunology, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Alireza Shafiei Division of Allergy and Clinical Immunology, Department of Pediatrics, Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran 2023 04 20 2023 09 20 Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children. This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission. In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge. The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2730 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2730/1987

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 420 429 EN Yan Zhou Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China Limin Zhou Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China Weizong Jin Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China Chenhui Qiu Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China Hualiang Jin Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China 2022 09 30 2023 08 03 Chronic allergen exposure can significantly induce p38 mitogen-activated protein kinase (MAPK) activation in asthma. p38 MAPK is involved in steroid resistance through phosphorylation of glucocorticoid receptors (GR) at S226. This study aims to investigate whether chronic allergen exposure can induce steroid resistance and whether it is associated with p38 MAPK activation in asthma. A mouse model of asthma was prepared by sensitizing and challenging mice with chronic ovalbumin (OVA) exposure. Key features of allergic asthma, encompassing bronchial hyperresponsiveness, pathology of lung tissues, cytokine profiles of inflammation in bronchoalveolar lavage fluid (BALF), and serum immunoglobulin (Ig)E concentration were evaluated. Furthermore, suppressive effects of corticosteroid on the splenocytes under stimulation of lipopolysaccharides, glucocorticoid receptor (GR) DNA binding ability of splenocytes, expression of GRα and phosphorylation of GR s226 in splenocytes, and p38 MAPK phosphorylation in splenocytes and lung tissues were determined. Chronic OVA exposure substantially induced airway hypersensitivity, leading to increased inflammatory infiltration in lung tissues. Additionally, it resulted in elevated levels of interleukin (IL)-4, IL-5, and IL-6 in BALF, as well as heightened levels of IgE in serum. Furthermore, OVA exposure substantially enhanced p38 MAPK phosphorylation in lung tissues. It also weakened the suppressive impacts of corticosteroids on splenocytes, impaired the GR DNA binding ability, and led to an enhanced phosphorylated state of GR S226 and p38 MAPK in splenocytes. Taken together, chronic allergen exposure contributes to steroid resistance in asthma, which is linked to an increased phosphorylated state of GR S226 and p38 MAPK. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3662 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3662/1970

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 430 439 Wen Cui Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Huan Zhou Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Ya-zun Liu Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Yan Yang Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Yi-zhong Hu Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Zhao-peng Han Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Jian-er Yu Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Zheng Xue Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China 2023 02 23 2023 09 26 Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)–dendritic cell (DC)–OX40L axis was investigated. A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively. Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased. Amygdalin thus regulates the Th1/Th2 balance through the TSLP–DC–OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3780 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3780/1992

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 482 494 EN Mohsen Nemati Bajestan Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Moein Piroozkhah Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Vahid Chaleshi Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Naser Ghiasi 2 Laboratory of Biological Complex Systems and Bioinformatics (CBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran Negar Jamshidi Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Reza Mirfakhraie Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hedieh Balaii Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Shabnam Shahrokh Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hamid Asadzadeh Aghdaei Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zahra Salehi Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Ehsan Nazemalhosseini Mojarad Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2022 12 05 2023 07 29  Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3731 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3731/1983

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 452 467 Behrouz Robat-Jazi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Mona Oraei Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Sama Bitarafan Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Seyed Alireza Mesbah-Namin Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ali Noori-Zadeh Department of Clinical Biochemistry, Faculty of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran Fatemeh Mansouri Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Karim Parastouei Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran Ali Anissian Department of Veterinary Pathology, Islamic Azad University, Abhar, Iran Mir Saeed Yekaninejad Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Ali Akbar Saboor Yaraghi 1Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2023 08 01 2023 09 18 Previous studies noted an imbalance in T helper (Th) 17 and regulatory T cells (Tregs) in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis animal model. calcitriol, vitamin D's active form, was found to ameliorate EAE symptoms by favoring Tregss over Th17 cells, suggesting immunomodulatory effects. This study aimed to assess calcitriol's impact on EAE manifestations and cytokine profile in mice. In this study, we recruited twenty-eight C57BL/6 mice and divided them into 4 groups: healthy controls, EAE, EAE with calcitriol treatment, and healthy mice with calcitriol treatment. CD4+ T cells were isolated from splenocytes using magnetic-activated cell sorting. Real-time polymerase chain reaction was employed to quantify the genes associated with Th9 cells (i.e., SPI1 encoding PU.1 and IL9 encoding interleukin [IL]-9). Moreover, the levels of IL-17 and transforming growth factor beta (TGF-β) were evaluated through enzyme-linked immunosorbent assay in the supernatant of CD4+ T cell culture stimulated by anti-CD3 and anti-CD28 antibodies for 72 hours. In the supernatant of CD4+ T cell cultures, the levels of interleukin-17 (IL-17) were significantly increased, while the levels of transforming growth factor beta (TGF-β) were decreased in the EAE Group compared to the healthy control group. Calcitriol treatment reversed these changes and attenuated EAE symptoms, as confirmed in hematoxylin and eosin, and luxol fast blue stains. Notably, calcitriol increased IL9 gene expression in both EAE and healthy mice.  This study provides further evidence of the anti-inflammatory effects of calcitriol and its role in attenuating EAE. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3892 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3892/1993

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 468 481 Behnaz Esmaeili Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran Hoda Khoshnevis Medical Genetic Ward, Imam Khomeini Hospital Complex (IKHC), School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Atefe Alirezaee Immunology, Asthma and Allergy Research Institute (IAARI), Tehran University of Medical Sciences, Tehran, Iran AND Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Abbas Shakoori Medical Genetic ward, Imam Khomeini Hospital Complex (IKHC), School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Zahra Pourpak Immunology, Asthma and Allergy Research Institute (IAARI), Tehran University of Medical Sciences, Tehran, Iran AND Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Hamid Chegini Department of Medical Laboratory Science, School of Allied Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran Zahra Ahmadinejad Department of Infectious Diseases, Liver Transplant Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 2022 12 03 2023 07 27 Many studies have evaluated the possible utility of cycle threshold (Ct) values as a predictor of Coronavirus disease 2019 (COVID-19) severity and patient outcome. Given the inconsistent results, we aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Ct values and disease severity, inflammatory markers, and outcomes in Iranian patients with COVID-19. A retrospective study of 528 patients with COVID-19 hospitalized from September 2020 to October 2021 was conducted. Demographic, clinical, and laboratory data of patients were retrieved from electronic medical records. Ct values were analyzed as a continuous variable after subcategorizing into 3 groups: low (Ct values<20), medium (Ct values 20 to 30), and high (Ct values>30). Of the 528 patients (45.1% female) aged 13 to 97 years, 109 patients had low Ct values, 312 patients had medium, and 107 patients had high Ct values. Patients with low Ct values were more likely to present with critical COVID-19, require invasive mechanical ventilation and develop complications such as acute respiratory distress syndrome and pneumonia. Furthermore, patients with low or medium Ct values were more likely to die compared to patients with high Ct values. Multivariate analysis showed that patients with low or medium Ct values were more likely to have severe COVID-19 compared with patients with high Ct values. The multivariate analysis also showed a higher risk of mortality in patients with low Ct values compared to patients with high Ct values, although this was not statistically significant. Our findings revealed that Ct values were an independent predictor of COVID-19 severity. The risk of mortality was higher in patients with low Ct values. However, further investigation is needed to address the correlation between Ct values and inflammatory factors.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3729 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3729/1988

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 5 2023 10 29 495 503 EN Mojdeh Soltani Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mahshid Vosoughi Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mazdak Ganjalikhani-Hakemi Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran AND Department of Immunology, Faculty of Medicine, Yedıtepe Unıversıty, Istanbul, Turkey Hoorieh Shapoorian Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Pezhman Beshkar Department of Laboratory Sciences, School of Allied Medical Sciences, Shahrekord University of Medical Sciences, Shahrekord, Iran Nahid Eskandari Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Behrooz Ghezelbash Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2023 04 26 2023 09 14 Programmed death ligand‑1 (PD‑L1) is a pivotal inhibitory checkpoint ligand known to induce T-cell exhaustion via interaction with the programmed death‑1 (PD‑1) receptor. Beyond this, PD-L1’s intrinsic signaling pathways within cancer cells warrant further exploration. This study aims to elucidate the effect of PD-L1 stimulation on the proliferation, survival, and apoptosis of acute myeloid leukemia (AML) cell lines. Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry. Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells. This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3819 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3819/1991