Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 1 11 Farnaz Aligolighasemabadi Department of Internal Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran AND Health Policy Research Centre, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran Majid Mirsadraee 3 Department of Internal Medicine, Medical School, Islamic Azad University, Mashhad Branch, Mashhad, Iran Mohammadamin Sadeghdoust Department of Internal Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran AND Health Policy Research Centre, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran Shadi Ghaffari Department of Physiology, Faculty of Biology, Islamic Azad University, Damghan Branch, Damghan, Iran Mohammad Sarafraz Yazdi Department of Internal Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran Saeed Naghibi Department of Radiology, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran Amirhossein Hashemi Attar Department of Radiology, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran 2022 03 04 2022 11 13 The purpose of this study was to evaluate the effect of 8 months of treatment with itraconazole on airway wall thickness in patients with severe persistent asthma. It was a double-blind, randomized, placebo-controlled clinical trial (IRCT20091111002695N9). Seventy-five subjects with severe persistent asthma received itraconazole (100 mg), prednisolone (5 mg), or placebo twice a day for eight months in three treatment groups (n=25 in each group). The primary objective was to improve the right upper lobe apical segmental bronchus (RB1) wall thickness percentage measured by high-resolution computed tomography scan of the lungs. Other morphometric measurements of RB1, asthma control test (ACT) score, presence of wheezing, dyspnea severity, rate of asthma exacerbation, fractional exhaled nitric oxide (FeNO), and expiratory volume in 1 second (FEV1) were set as the secondary outcomes. Wall thickness percentage reduced significantly from 46% to 43.7% from pre- to post-treatment in the itraconazole-treated subjects. Similarly, lumen area and radius increased significantly in both the prednisolone and itraconazole groups. Itraconazole led to a significant improvement in wheezing, dyspnea severity, FEV1, ACT score, and FeNO. Although prednisolone was also effective in improving pulmonary function tests and ACT scores, it was associated with significantly more side effects than itraconazole. Long-term treatment with itraconazole resulted in a significant reduction in bronchial wall thickness and improvements in clinical findings and pulmonary function tests. Thus, itraconazole could be a helpful add-on treatment option for severe persistent asthma patients to achieve better disease control. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3474 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3474/1909

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 12 24 Shima Rasouli Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Jalal Heshmatnia Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Nariman Mosaffa Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Majid Marjani Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Esmaeil Mortaz Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran 2022 08 20 2022 09 16 Fibrosing pneumonia (FP) is classified into usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), each having its own etiology and prognosis. Both types of FP are progressive and chronic conditions with distinct etiologies. Cytokines and inflammatory mediators play critical roles in the pathogenesis of FP. Among them, the role of transforming growth factor beta-1 (TGF-β1) and modulators triggering fibrosis are not well understood. In this study, the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) as a stimulator for the production of TGF-β1 and also CD4+CD25+Foxp3+ regulatory cells were investigted in FP patients. Sixteen UIP, 14 NSIP and 4 pulmonary fibrosis following Mycobacterium tuberculosis (TB) infection patients, were compared with 12 healthy controls. The frequency of blood CD14+TGF-β1+ and CD14+TREM1+-gated monocytes and CD4+CD25+Foxp3+ regulatory T cells (Treg), as well as the plasma levels of TGF-β1 and IL‑10 were measured. Fibrosis patients compared to healthy controls had a greater frequency of CD14+TGF-β1+ [15.9 (0.2-88.2) vs. 0.6 (0.2-11.0)] and CD14+TREM1+ [21.1 (2.3-91.2) vs. 10.3 (3.1-28.6)]-gated monocytes, and CD4+CD25+Foxp3+ [1.2 (0.3-3.6) vs. 0.2 (0.1-0.4)]-gated lymphocytes. Plasma TGF-β1 were also significantly increased in patients with fibrosis compared to healthy controls [9316.2 (±5554.4) vs. 3787.5 (±2255.6)]. These results confirm the importance of TGF-β1 and TREM1 in pulmonary fibrosis. It seems that this reciprocal cycle in healthy people is modulated by the production of IL‑10 by Treg cells, thus limiting fibrosis, as observed in patients following TB infection. Further investigations are recommended to evaluate possible immunomodulatory mechanisms defects in pulmonary fibrosis.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3637 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3637/1927

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 25 33 Fereshteh Beigmohammadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Saeed Aslani Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran ‎ Ali Javinani Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran ‏ ‏Shayan Mostafaei Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Mehran Pournazari Clinical Research Department Center, Imam Raza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Baharak Tasorian Division of Rheumatology, Department of Internal Medicine, Arak University of Medical Sciences, Arak, Iran Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran Asghar Hajiabbasi Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran Habib Zayeni Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran Alireza Khabbazi Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Irandokht Shenavar Masooleh Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran Zahra Tamartash Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Vojdanian Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2021 11 03 2022 10 24 Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients. This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant. Among the KIR and HLA genes, a significant decrease was detected in the frequency of 2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95% CI=0.05–0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA. The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3394 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3394/1916

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 34 45 Khadijeh Chakamian Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran Behrouz Robat-Jazi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Abdorreza Naser Moghadasi Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Fatemeh Mansouri Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Masoumeh Nodehi Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Elahe Motevaseli Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Izad Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Saeed Yekaninejad Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mahdieh Shirzad Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran Kiana Bidad 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 Bita Ansaripour Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Ali Akbar Saboor-Yaraghi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2021 10 27 2022 11 24 T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor β (TGF-β), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-β and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3293 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3293/1921

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 46 61 EN Majdedin Ghalavand Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Ruholiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1). Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls. Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3043 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3043/1718

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 413 422 Dragana Jovanovic Clinic of Allergy and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia Aleksandra Peric-Popadic Clinic of Allergy and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia AND Faculty of Medicine, University of Belgrade, Belgrade, Serbia Sladjana Andrejevic Clinic of Allergy and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia AND Faculty of Medicine, University of Belgrade, Belgrade, Serbia Maja Stojanovic Clinic of Allergy and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia AND Faculty of Medicine, University of Belgrade, Belgrade, Serbia Branka Bonaci-Nikolic Clinic of Allergy and Immunology, University Clinical Centre of Serbia, Belgrade, Serbia AND Faculty of Medicine, University of Belgrade, Belgrade, Serbia 2020 08 12 2021 04 06 Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2933 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2933/1726

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 423 431 Maryam Khoshkhui Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Karsten Weller Department of Dermatology and Allergy, Dermatological Allergology, Allergie-Centrum-Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany Javad Fadaee Department of Pediatrics, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran Marcus Maurer Dermatological Allergology, Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany Farahzad Jabbari Azad Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Maryam Emadzadeh Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran 2020 10 11 2021 05 16 The urticaria control test (UCT) is a patient-reported outcome measure (PROM) for chronic urticaria (CU) patients. As a Persian version of the UCT was not available, the present research aimed to develop such a version, to test its reliability and validity as well as to evaluate urticaria control among Persian-speaking patients. This research was conducted at the Urticaria Centre of Reference and Excellence (UCARE) of Ghaem Hospital, Mashhad, Iran. In a first step, a linguistically validated Persian version of the UCT was developed through a structured forward and backward translation process and subsequent cognitive debriefing interviews. In a second step, the Persian version of the UCT was completed by 100 well-characterized CU patients together with two anchor instruments, the Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and the urticaria activity score (UAS), to obtain information on its internal consistency reliability and convergent validity. The Persian version of the UCT was found to have acceptable internal consistency reliability with a Cronbach's alpha coefficient of 0.68. In addition, the results obtained with the Persian UCT correlated with the CU-Q2oL total score (-0.48, p<0.001) and the UAS (-0.404, p˂0.001), suggesting convergent validity. Virtually all patients had poorly controlled CU (UCT<12). A Persian version of the UCT is now available and may help to improve the assessment and monitoring of disease control in Persian-speaking CU patients and to optimize treatment decisions. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2998 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2998/1725

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 432 440 Jia Li Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Houyong Kang Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Suling Hong Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Yang Shen Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2020 07 17 2020 12 26 Patients with chronic rhinosinusitis (CRS) and allergic rhinitis (AR) (CRSwAR) have a more severe condition with a higher rate of recurrence after endoscopic sinus surgery (ESS). This study aimed to explore the effect of specific subcutaneous immunotherapy (SCIT) and nasal irrigation on CRSwAR after ESS. Sixty-four patients who were diagnosed as CRSwAR and received ESS were enrolled and divided into groups A, B, and C to receive different postoperative treatment strategies (conventional medication, medication with nasal irrigation, and medication with nasal irrigation and SCIT), and their prognosis was evaluated by scoring, electron microscopy, and inflammatory factors. One year after ESS, the recurrence rate of group C was significantly reduced; and the scoring from baseline was significantly different among the three groups, which of group C were the best. The epithelium arrangement, cilia morphology, and inflammation of nasal mucosa in each group were better than those in the preoperative state; and those in group C were the best. After one year, the expression levels of eosinophil cationic protein (ECP), interleukin (IL)-8, and IL-17 in group B were lower than those of group A; and the expression levels of ECP, IL-8, IL-25, IL-33, IL-17 in group C were lower than those in group A. SCIT combined with nasal irrigation can improve the patients' symptoms and quality of life, promote the epithelialization of the mucosa in the surgical cavity, regulate the local immune response of the nasal cavity; thus improve the prognosis of patients with ESS after 1 year. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2901 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2901/1713

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 441 452 Saman Yousefi Saqqezi Department of Sport Sciences, Shahrekord University, Shahrekord, Iran Akbar Azamian Jazi Department of Sport Sciences, Shahrekord University, Shahrekord, Iran Roohullah Hemmati Department of Biology, Shahrekord University, Shahrekord, Iran AND Biotechnology Research Institute, Shahrekord University, Shahrekord, Iran Nahid Jivad Department of Neurology, Shahrekord University of Medical Sciences, Shahrekord, Iran 2020 10 13 2021 04 18 Some antimicrobial peptides (AMPs), microRNAs (miRs), and Toll-like receptor 4 (TLR-4) are involved in autoimmune diseases, which may be affected by exercise training. The purpose of this study was to investigate the effect of an eight-week combined exercise training (aerobic and resistance) on the expression of inflammatory factors, including, human beta-defensin-2 (hBD-2), cathelicidin (LL-37), TLR-4, miR-23b, miR-155, and miR-326 in women with relapsing and remitting multiple sclerosis (RRMS), which has not been investigated yet. Twenty-three women (20-40 years) with RRMS were randomized into the combined training (CT) and control (CON) groups. The CT group subjects completed eight weeks of supervised CT using a treadmill and stationary bicycle for aerobic exercise and weight machines for resistance exercise. The expression levels of hBD-2, LL-37, TLR-4, miR-23b, miR-155, and miR-326 were measured by real-time polymerase chain reaction (RT-PCR) at the baseline and end of the study. Although the expression of hBD-2 and miR-23b decreased in both CT and CON groups, the reduction was lower in the CT group than in the CON group (p=0.001). The expression of LL-37 in the CT group remained unchanged, but that of the CON group increased; thus, the between-group difference was significant. Although the TLR-4, miR-155, and miR-326 expression increased in both groups compared to the baseline, the increase in the CT group was lower than the CON group. Our results showed that the combined training might improve inflammatory symptoms by affecting the expression of some AMPs, miRs, and TLR-4 in patients with relapsing and remitting multiple sclerosis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3000 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3000/1714

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 453 464 Jafar Karami Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran Ali-Akbar Delbandi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Mehdi Shekarabi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Mohammad Naghi Tahmasebi Department of Orthopedics, Division of Knee Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Arash Sharafat Vaziri Division of Knee Surgery, Department of Orthopedics, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Maryam Akhtari Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mohammad Javad Mousavi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Department of Hematology, Faculty of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2021 01 01 2021 02 04 Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3080 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3080/1724

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 465 472 EN Nearmeen Rashad Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt Reham El Shabrawy Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt Ahmed Radwan Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University, Zagazig, Egypt Reem Allam Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Egypt Rehab Abdul-Maksoud Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt Magda Sherif Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt 2020 08 31 2021 03 15 Diagnosis of unexplained infertility (UEI) is made by exclusion and a relatively common problem that affects couples worldwide. Unfortunately, it is a not uncommon for females to suffer from Hashimoto's thyroiditis (HT). Interferon-gamma (IFN- γ) has a central key role in HT and in the ability to conceive. We aimed to estimate serum IFN- γ level and its expression profile in Egyptian women with HT and assess their possible association with UEI. In this study, we examined 120 women with HT. We evaluated fertility in all patients; female patients who suffer from UEI were detected. Diagnosis of HT was based on the clinical data and the laboratory measures, enzyme-linked immunosorbent assay was used to measure serum IFN- γ, and the expression of IFN-γ messenger ribonucleic acid (mRNA) was assayed by real-time polymerase chain reaction (PCR). According to the results of this study, 37.5 % of the studied females who suffered from HT were diagnosed with UEI. The serum level of IFN-γ and its gene expression showed a significant positive correlation with thyroid-stimulating hormone (TSH) and thyroid autoantibodies. However, a negative correlation was found with anti-müllerian hormone (AMH), free T4 (FT3), and free T4 (FT4). Analysis by linear regression revealed that TSH and FT3 were associated with serum level of IFN-γ; while FT3 was associated with IFN-γ gene expression. We concluded that both are valued markers in diagnosing UEI in female patients suffering from HT. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2917 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2917/1722

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 473 483 Alireza Farrokhian Department of Cardiology, Kashan University of Medical Sciences, Kashan, Iran Mahtab Miraftab Students’ research center, Kashan University of Medical Sciences, Kashan, Iran Minoo Chenari Students’ research center, Kashan University of Medical Sciences, Kashan, Iran Hossein Akbari Social Determinants of Health (SDH) Research Center, Kashan University of Medical Sciences, Kashan, Iran Hassan Nikoueinejad Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Effat Naimi Chemical Injuries Research Center, System Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2020 03 14 2021 02 07  Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2744 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2744/1720

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 4 2021 08 07 484 493 Fahimeh Sadat Emami Mahmoudabadi Department of Biology, Faculty of Basic Science, Shahed University, Te