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 1735-1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Karim Shamsasenjan Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Elham Safarzadeh Department of Microbiology and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Tohid Kazemi Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran Ali Akbar Movassaghpour Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2021 01 16 2021 06 02 Many studies have been performed about regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) and their application in different treatment approaches. The present study aimed to investigate the immunomodulatory effect of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on the gene expression profile of cytokines in stimulated T-lymphocytes. For this purpose, MSCs were isolated from umbilical cord blood samples and cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. The nature of MSCs was identified by flow cytometry analysis and differentiation to the adipocyte and osteocyte lineage. Moreover, to investigate the immunomodulatory effects of MSCs on T cells, a co-culture system was designed and expression levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β) genes were measured; using the real-time polymerase chain reaction (RT-PCR) technique. Our results demonstrated the ability of MSCs to differentiate into adipocyte and osteocyte lineages. Further investigation also displayed that although UCB-MSCs could significantly reduce the expression of pro-inflammatory cytokines like IL-2, IL-6, IFN-γ, and TNF-α in activated T-lymphocytes, they noticeably potentiated the expression levels of IL-4, IL-10, IL-13, and TGF-β in the co-culture setting. In conclusion, UCB-MSCs have immunomodulatory effects on activated T-lymphocytes in favor of anti-inflammatory responses. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3101 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3101/1766

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 6 2021 12 08 721 733 EN Saeede Soleimanian Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Ramin Yaghobi Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Mohammad Hossein Karimi Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Bita Geramizadeh Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Jamshid Roozbeh Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2021 05 25 2021 07 23 Natural killer (NK) cells are essential for controlling certain viral infections, including cytomegalovirus (CMV). In particular, the importance of NK cells in the context of CMV infection is underscored by the adaptive capabilities of these cells. Evidence suggests that some viruses can directly interfere with NK cell compartments and their activation and lead to shape-shifting the NK cell receptor repertoire. Still, it remains unknown whether the CMV can interact with NK cells without intermediaries. Here, we examined whether the direct effects of CMV lysate alter phenotypical properties of NK cells. To investigate this issue, NK cells were isolated from the blood of CMV seropositive healthy donors by negative magnetic separation. Isolated NK cells were cultured in the presence of CMV lysate and analyzed for the expression of NKG2A, NKG2C, and CD57 by FACS caliber. The results showed that NKG2C expression is significantly upregulated in the presence of CMV lysate compared to without stimulated group (mean increase, 6.65 %; 95% CI, 0.2582 to 13.02; p=0.043; R square: 0.38). Likewise, results have shown a significant decrease in the frequency of NKG2A+CD57- NK cell subsets (p=0.005; 95% CI, -13.49 to -3.151; R square: 0.5957) in the stimulated group compared to without stimulated ones. According to these results, CMV may drive a direct influence on NK cell receptor repertoire, including the expansion of NK cells expressing NKG2C receptor, which is needed for further studies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3235 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3235/1748

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 6 2021 12 08 734 739 Ali Kouhi Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sahar Shakeri Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Nasrin Yazdani Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Niloufar Shababi Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Anita Mohseni Otorhinolaryngology Research Center, Amir A'lam Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Alireza Mohseni Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Sadr Molecular Immunology Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran Mahsa Mohammad Amoli Otorhinolaryngology Research Center, Amir A'lam Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Arezoo Rezaei Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran 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 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK 2020 07 10 2021 08 02 Meniere’s disease (MD) is known as a rare chronic disorder of the inner ear with elevated serum levels of pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, Interleukin (IL)-1, and IL-6. This study aims to evaluate genes polymorphism in some pro-inflammatory cytokines in a group of Iranian MD patients compared to the healthy controls. In this case-control study, 25 MD patients and 139 healthy controls were enrolled. DNA was extracted from blood samples, and single nucleotide polymorphisms were detected using polymerase chain reaction with sequence-specific primers assay. MD patients and controls were examined in terms of allele, genotype, and haplotype frequency of pro-inflammatory cytokine genes. Only the frequencies of alleles A/G at position -238 in the promoter of the TNF-α gene differed significantly between MD patients and healthy controls. G to A allele ratio was 23 and 3.6 in MD and controls, respectively. In individuals with MD, genotype GG was found to be significantly more prevalent at position -238 of the TNF-α gene promoter sequence. In addition, the heterozygote AG variant of -238 A/G TNF-α gene polymorphism was lower in MD patients than controls. Compared to the control group, the haplotype TNF- (-308, -238) AG was higher in MD patients, although not statistically significant. This is the first study that we know of that evaluates the frequencies of pro-inflammatory cytokine genes in an Iranian MD sample. This study shows the association between TNF-α and susceptibility to MD. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2898 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2898/1762

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 6 2021 12 08 740 750 Shermineh Heydari Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ladan Kashani Infertility Ward, Arash Women’s Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mehrdad Noruzinia Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2021 02 07 2021 05 30 Endometriosis is a common, chronic, inflammatory disorder in women, characterized by the presence of endometrial tissue outside the uterus cavity. The disease affects ~10% of women during their reproductive age. There is some debates on the pathogenesis of endometriosis and its mechanism among the scientists; therefore, different hypotheses have been suggested. Acc