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 1735-1am Esmaeelzadeh Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran 2023 03 06 2023 08 22 Multiple sclerosis (MS) is an inflammatory disorder impacting the central nervous system, with cytokines significantly influencing its pathogenesis. This study investigates the effect of curcumin and its semisynthetic derivative F-curcumin on cytokine gene expression in autoimmune encephalomyelitis (EAE) mouse models of MS. We assessed the expression levels of specific cytokines including interleukin (IL)-1β, IL-4, IL-10, IL-17, interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β), alongside key transcription factors for helper T cells (T-bet, GATA-3, RORγt, and FoxP3) in both the spinal cord and spleen. Treatment with curcumin and F-curcumin significantly ameliorated the severity and onset of EAE. Notably, mice administered with either compound showed a substantial decrease in the expression of genes encoding IL-1 (2 folds), IFN-γ (2 and 4 folds), and IL-17 (2.5 and 3.5 folds), alongside a marked increase in TGF-β (7 folds) and IL-10 (4 and 6 folds) levels. Additionally, the gene expression of T cell-derived transcription factors nearly mirrored the changes observed in pro-inflammatory and anti-inflammatory cytokines across the groups. The F-curcumin-treated group exhibited more pronounced results. In conclusion, curcumin and F-curcumin significantly modulate cytokine gene expression during EAE induction, potentially alleviating inflammation in MS, with F-curcumin showing a more substantial effect. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3787 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3787/2017

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 588 599 Elham Mashayekh 1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Arezou Khosrojerdi Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran Ahmad Zavaran Hosseini 1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Sara Soudi 1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2023 08 21 2023 11 28 Pathogen recognition receptors (PRRs), which play a crucial role in responding to pathogens, affect the function of mesenchymal stem cells (MSCs). One important group of PRRs is the toll-like receptors (TLRs). When PRRs are activated, they can alter the expression of specific surface markers, the ability of MSCs to differentiate, and the types of substances they secrete. These modifications in MSC function may have unexpected consequences for patients. In this study, we examined how Leishmania major (L. major) promastigotes affect the properties of MSCs. MSCs were isolated from adipose tissue and categorized into two groups: one group left untreated and the other group exposed to L. major. Giemsa staining was employed to accurately quantify the number of parasites that entered the cells. After 72 hours, real-time polymerase chain reaction was utilized to assess the expression of TLRs. Additionally, the flow cytometry technique was used to evaluate the expression of surface markers on the MSCs. Our results showed that MSCs can engulf parasites and increase the expression of TLR4 and TLR6. The pro-inflammatory cytokine increased, and the transforming growth factor-β decreased significantly. The parasite exposure increased reactive oxygen species production. Additionally, the percentage of cluster differentiation (CD) 73 decreased, and the mean fluorescent index of CD29 and CD73 was down-regulated by L. major. Exposure to parasites diminishes the immunomodulatory capacity of MSCs. This discovery holds significance for the application of MSCs in addressing parasite infections and underscores the need for additional research to enhance their therapeutic effectiveness. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3905 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3905/2002

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 600 603 Eduardo Liquidano-Perez Immunology Service, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico Mariana Carmona Berrón Immunology Service, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico Rosa Itzel Carrillo Nieto Immunology Service, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico Celso Corcuera Delgado Pathology Department, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico Lizbeth Blancas Galicia Immunodeficiencies Unit, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico Selma Scheffler Mendoza Immunology Service, National Institute of Pediatrics, Secretariat of Health Mexico, Mexico City, Mexico 2022 03 08 2023 07 26 Chronic granulomatous disease (CGD) presents with granuloma formation and lethal infections. It is inherited in an autosomal or X-linked recessive pattern. We describe a 10-month-old patient with a fatal secondary HLH as a CGD primary manifestation. We carried out an autopsy and found noncaseating granulomas, an aspergilloma in the lung, and hemophagocytosis. We performed a DHR assay on the patient’s mother and grandmother, showing a bimodal pattern conclusive of X-linked CGD. Thus, our definitive diagnosis was CGD complicated by macrophage activation syndrome. CGD is caused by phagocytes’ inability to control pathogens, resulting in granulomas. Secondary HLH is a severe complication and could be characterized by the proliferation of macrophages and T lymphocytes and the production of proinflammatory cytokines. The early suspicion of this presentation helps establish a specific treatment, and the study of the carriers helps determine the etiology. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3480 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3480/2018

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 604 608 EN Linxin Liu Department of General Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China Haoxian Gou Department of Hepatobiliary Pancreatic Surgery, School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China Yongfa Liu Department of General Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China Shuai Hu Department of General Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China Xiaoli Yang The Affiliated Hospital of Department of General Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaMedical University Bo Li Department of General Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 2022 11 11 2023 10 20 Kimura disease (KD), also known as eosinophilic lymphogranuloma, is a rare chronic inflammatory or allergic disease. It can present with immune-related diseases such as nephrotic syndrome, asthma, and ankylosing spondylitis. In this study, we report a case of KD combined with immunoglobulin A nephropathy that first presented as a mass in the inguinal region, followed by recurrent renal involvement. Previous reports suggested that renal involvement caused by KD was due to direct infiltration of eosinophils; however, in this case, no eosinophil infiltration was found in the renal tissue after renal biopsy. This observation reminds us to approach the case from an immune-related molecular perspective to investigate the exact cause of renal damage due to KD.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3705 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3705/1996

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 609 612 Ximena León-Lara Immunodeficiencies Laboratory, National Institute of Pediatrics, Mexico City, Mexico Susana García-Pavón Osorio Military Medical Offices, Mexico City, Mexico Sara Espinosa Padilla Immunodeficiencies Laboratory, National Institute of Pediatrics, Mexico City, Mexico Lizbeth Blancas-Galicia Immunodeficiencies Laboratory, National Institute of Pediatrics, Mexico City, Mexico 2023 09 14