Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 249 254 Mohammad Bemanian Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Saba Arshi Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Mohammad Nabavi Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Mohammad Vafaee-Shahi Pediatric Growth and Development Research Center, Iran University of Medical Sciences, Tehran, Iran Morteza Fallahpour Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Sima Shokri Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Afshin Rezaeifar Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran Hossein Shahzadi Department of Pediatric cardiology, Iran University of Medical Sciences, Tehran, Iran Fatemeh Atashrazm Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran 2020 05 16 2020 12 08 Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare primary immunodeficiency disorder characterized by recurrent infections and low immunoglobulin levels due to variable combined immunodeficiency, and centromeric region instability, and facial dysmorphism. We describe a 12-year-old boy with recurrent respiratory tract infections, facial anomalies, scoliosis, and psychomotor retardation. He had recurrent pneumonia with low serum IgG and IgM levels during infancy and preschool age. Later at the age of 10, he developed recurrent ear infections. An IgA and IgM deficiency was found accompanied by a normal B-cell and T-cell count as well as an impaired candida-induced T-cell proliferation. Further evaluations revealed a missense mutation in the DNMT3B gene on chromosome 20. Chromosomal analysis showed a sunburst multi-radial feature on chromosome 1, which is a hallmark of ICF syndrome. The genetic mutation and chromosomal abnormality along with clinical findings are compatible with the diagnosis of ICF syndrome. To the best of our knowledge, this is the first time that scoliosis is observed in an ICF patient. The additional variable clinical symptoms in the case were the presence of spastic gait as well as hypogammaglobulinemia with immunoglobulin isotype switch at different ages. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2813 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2813/1672

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 129 139 Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hassan Abolghasemi Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Parisa Naseri Research Center for Social Determinants of Health, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abdol Majid Cheraghali Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran Mohammad Javad Soltanpoor Clinical and Molecular Laboratory, Baqiyatallah Hospital, Baqiyatallah University of Medical Sciences, Tehran, Iran Abbas Ali Imani Fooladi Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2020 06 01 2020 12 08 Containment of pandemic infections mainly depends on prompt identification of carriers, achievable through strict surveillance and truthful diagnostic testing. Although molecular identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard method, its low sensitivity and long turnaround time are among major concerns. In this retrospective single-center study, we reviewed the results of the lymphocyte and neutrophil counts of 1450 Iranian patients with coronavirus disease 2019 (COVID-19) recruited at Baqiyatallah Hospital, Tehran, Iran. Of 1450 patients, 439 cases (30.3%) were polymerase chain reaction (PCR) negative; further emphasizing that getting negative molecular testing is not as reliable as a positive result. While the lymphocyte count in cases with less than 50 years old was 1.8×103/µL (1.2-2.5), it was 1.47×103/µL (0.84-2.16) in the older group (p<0.001). Also, men experienced lower lymphocytes as compared to women (1.53×103/µL vs 1.76×103/µL; p=0.002). Of particular interest, the lymphocyte count in the PCR-negative cases was 1.77×103/µL (0.98-2.45) which was significantly higher than its count in their positive counterparts (1.53×103/µL; p=0.004). Unlike lymphocytes, sex and PCR did not significantly affect the number of neutrophils. The odds ratio for neutrophilia in patients aged older than 50, either with a negative or a positive PCR, was 2.46 and 2.23, suggesting old age as the most significant associated factor. The number of lymphocytes along with increased neutrophil count may probably serve as simple, rapid, and economical biomarkers, and are seemingly appropriate items that should be taken into account in the identification of patients with COVID-19, especially those aged more than 50. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2849 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2849/1683

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 244 248 Ahmad Hormati Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran AND Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran Hossein Poustchi Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mohammad Reza Ghadir Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran Saeede Jafari Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran Narges Jafari Health center, Qom University of Medical Sciences, Qom, Iran Abdolreza Ashtari Constituent and Technical in Charge of Kimia Pathological and Medical Laboratory, Qom, Iran Sajjad Ahmadpour Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran 2020 06 22 2021 04 11 Coronavirus disease 2019 (COVID-19) is a worldwide public health problem that has attracted much attention due to its clinical findings. Measurement of IgG and IgM antibodies is of great importance for researchers and it will help to develop a new diagnostic and therapeutic method in clinical care. In this cross-sectional study, we aim to measure the IgG and IgM antibody levels in 401 suspected COVID-19 volunteers. We also measure the time duration for the appearance of IgG and IgM antibodies from the onset of symptoms to sampling time. Of 401 participants enrolled in the study, 255 (63.59%) were healthy, 79 (19.70%) were a carrier, 59 (14.71%) were cured and 8 (1.99%) were borderline. Of 142 subjects diagnosed with COVID-19, 41 (28.87%) presented with gastrointestinal (GI) symptoms, 83 (58.45%) had no GI symptoms, and 18 (12.68%) were asymptomatic. According to our findings, the measurement of IgG and IgM antibodies will provide the tool for the diagnosis of COVID-19 and significantly boost research into novel diagnostic and therapeutic approaches. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2867 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2867/1697

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 255 259 Michael Makris Second Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece Christos Fokoloros Second Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece Anna Syrmali Second Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece Zoi Tsakiraki Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece Vasileia Damaskou Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece Evangelia Papadavid Second Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece 2020 06 09 2020 12 22 Generalized bullous fixed drug eruption (GBFDE) is a specific variant of fixed drug eruption that belongs to severe cutaneous adverse reactions (SCARs) and its diagnosis is based mainly on clinical course and especially on the reoccurrence of typical bullous lesions in previous and new sites after re-administration of the offending drug. We present a well-documented case of fluconazole-induced GBFDE, with a positive patch test to fluconazole (30% weight/volume preparation) and clinical tolerance to itraconazole proven by negative oral provocation. Even in SCARs, patch testing represents a useful diagnostic tool, while oral provocation remains the gold standard in cases that an alternative but the chemically relevant drug must be administered. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2856 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2856/1689

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 140 146 Ali Mostafaei Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Ophthalmology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Morteza Ghojazadeh Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran Sakineh Hajebrahimi Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Urology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Nasrin Abolhasanpour Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran Hanieh Salehi-Pourmehr Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran 2020 07 23 2020 12 24 The coronavirus disease 2019 (COVID-19) pandemic in Iran is part of the worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aimed to demonstrate the clinical characteristics of patients affected by COVID-19, in our tertiary teaching hospital. Medical records and compiled data of 668 patients with suspected COVID-19 were obtained retrospectively between January to April 2020. The present study outcomes included demographic features of infected patients, underlying diseases and conditions, the relationship between the results of reverse transcription-polymerase chain reaction (RT-PCR) or CT-scan with the manifestations of the disease, mortality rate, and age distribution of fatalities among men and women. The median age of hospitalized patients was 63 years old (from 18 to 94). The patients’ chief complaints in the admission time were cough, dyspnea, fever, and gastrointestinal problems, respectively. Hospitalized patients' common comorbidities were hypertension (HTN), and cardiovascular disease (CVD) (24%), diabetes mellitus (DM) (21.5%), asthma, or chronic obstructive pulmonary disease (COPD) (6%), or other underlying diseases (15.5%). One-third of patients had no comorbidity according to the data of medical records. In hospitalized patients, 169 (84.5%) had positive RT-PCR, and 156 (78%) had positive chest CT findings. The mortality rate of males was higher than females (66.3% vs. 33.3%) and in patients with positive RT-PCR compared to patients with positive chest CT-scan findings. The majority of deaths had a history of DM or HTN/CVD in their medical records. The chief complaint of patients was cough. DM and HTN or CVD were the common underlying disease related to death in hospitalized cases. Besides, the hospitalization and mortality rate in males was higher than in females. About 87% of dead hospitalized cases had positive RT-PCR results, and this rate was 82% for chest CT results. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2908 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2908/1698

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 147 159 Syed Shahid Bukhari Department of Zoology, Environmental Health and Wildlife Lab, University of the Punjab, Lahore, Pakistan Zulfiqar Ali Department of Zoology, Environmental Health and Wildlife Lab, University of the Punjab, Lahore, Pakistan 2020 07 03 2020 12 22 Airborne bioaerosols and particulate matter (PM) have been associated with asthma occurrence. Due to the adverse indoor environment and the absence of any baseline data for asthmatic patients of Pakistan, this study was aimed to establish a correlation between microflora and PM of residential microenvironments of asthmatic patients. This pilot study was conducted in different residential settings of asthmatic patients registered in the Jinnah hospital, Lahore. The characterization of PM (PM01, PM2.5, PM10) and bioaerosols were carried out in the houses of fifty patients that were categorized into four groups; A-large (418.06 m2), B-medium (211 m2), C-medium (104 m2), and D-small (62.71 m2) houses. The PM concentrations were monitored; using the DustTrack8533 aerosol monitor and the bioaerosols were characterized up to the Genus; using the culture-based method and biochemical testing. The bioaerosols were sampled; using the expose plate method and were analyzed using morphological features and biochemical tests. Eleven types of fungi and seven bacterial types were found in the air samples. The tendency of asthma occurrence is linked with higher Alternaria spp and Aspergillus spp. The mean indoor readings of PM01, PM2.5, PM10 were highest in D-category (331.75, 342.5, and 502.33 respectively). Moreover, the highest bacterial 9618 CFU/m3) and fungal levels (3092 CFU/m3) were also seen in D-category. According to two-way ANOVA, bacterial concentration was significantly different among the four groups while fungi concentration was non-significant (p<0.05). Pearson correlation showed a significant positive correlation among bioaerosol counts, relative humidity, and temperature. Moreover, a positive significant correlation was also observed among PM, bioaerosols, and temperature (p<0.01). The multiple regression analysis confirms temperature as a significant predictor of bioaerosols and bacterial and fungal concentrations were observed to be a significant predictor for PM. Hence monitoring the PM levels could help in maintaining the indoor microenvironment for sensitive asthmatic patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2887 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2887/1696

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 160 168 EN Sahar Rostami Hir Department of Medical Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Zahra Alizadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Marzieh Mazinani Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Maryam Mahlooji Rad Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Asthma and Allergy Center, Tehran Medical Sciences Branch of Academic Center for Education, Culture and Research (ACECR), Tehran, Iran Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Anoushiravan Kazemnejad Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ahmad Zavaran Hosseini Department of Medical Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mostafa Moin Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran 2020 07 20 2020 12 22 Exosomes are extracellular vesicles that are involved in intracellular communication and different biological processes. Recently, the importance of microRNAs (miRNAs) in exosomes has been considered as biomarkers in asthma diagnosis. This study aimed to determine the expression of selective miRNAs from plasma-derived exosomes in moderate and severe asthmatic patients compared with healthy controls. Forty-six subjects including 22 patients with severe and mild to moderate allergic asthma and 24 healthy controls have entered this study. MiRNAs were extracted from the plasma exosomes and selective miRNAs (miR-21, miR-16, miR-Let7, miR-148a, miR-155, miR-125, miR-150, miR-146a, miR-223, miR-126) expressions levels were determined; using quantitative polymerase chain reaction (qPCR). In this study, we found a significant up-regulation of miR-223 and miR-21 in moderate asthmatic patients compared to the healthy controls (p=0.002, p=0.006). MiR-223 and miR-21 had the probability of 83% and 76% diagnosis estimation in moderate asthmatic patients respectively. Therefore, they could be used as biomarkers in these patients.  No expression of miR-125, miR-126, and miR-155 was found in plasma exosomes by qPCR in this study. The other miRNAs had no significant expression between different groups. Based on our findings,miR-223 and miR-21 may be considered biomarkers or used for targeted immunotherapies in asthma. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2906 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2906/1694

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 169 177 EN Baharak Chehardoli Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran Mona Nadi Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran Ali Khamis Abadi Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Azam Kia 3Basic Science School, East Tehran Branch, Payame Noor University, Tehran, Iran. Alireza Shahriary Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Jafar Salimian Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2020 10 11 2020 12 30 Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1), and Interleukin-1β (IL-1β)  genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1 (~4 fold) genes (p<0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. The present study concludes that curcumin as an anti-inflammatory agent may have beneficial immunomodulatory effects following CEES exposure. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2999 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2999/1686

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 178 187 Naeim Ehtesham Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Behrang Alani Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran Deniz Mortazavi Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Sara Azhdari Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Iran Taiebe Kenarangi Student Research Committee, Faculty of Statistics, University of Social Welfare and Rehabilitation Science, Tehran, Iran Emran Esmaeilzadeh School of Medicine, AJA University of Medical Science, Tehran, Iran Bahram Pakzad Department of Internal Medicine, Division of Rheumatology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran 2021 01 11 2021 02 27 The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3094 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3094/1693

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 188 197 EN Parisa Esmaeili Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran AND Department of Epidemiology, Pasteur Institute of Iran, Tehran, Iran Elham Rostami Department of Biology, School of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran Arefeh Akbarijavar Graduated from Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran Alireza Akbari Meyestani National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran. Iran Hamed Bashiri Department of Laboratory Sciences, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran Mohammad Ali Rezaee Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran AND Department of Medical Laboratory Sciences, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran Shohreh Fakhari Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran AND Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran 2019 11 10 2020 09 27 Gluten sensitivity contributes to various degrees of neurological manifestations and neurodegenerative immunological changes. We investigated the experimental features of anti-gliadin immune responses in the central nervous system (CNS) of mice. Female C57BL6 mice were divided into three groups. Mice immunized with complete Freund's adjuvant (CFA) or gliadin emulsified in CFA, and the control group received phosphate-buffered saline (PBS). Immunohistochemistry, hematoxylin-eosin, and Luxol fast blue staining were performed on the sections. The serum levels of interleukin (IL)-17 and interferon-gamma (IFN-γ) were measured using enzyme-linked immunosorbent assay (ELISA). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the mRNA levels of chemokine (C-X-C motif) ligand-2 (CXCL-2), C-C motif chemokine ligand-2 (CCL-2), and CXCL-10.  In gliadin+CFA immunized mice, the microscopic lesions included perivascular edema, focal-microgliosis, and acute neuronal necrosis in the cortex, subcortical, Purkinje cell layer, and ventral horn of the spinal cord. While extravasation of anti-IgG antibodies and selective targeting of Purkinje cells were observed in gliadin+CFA immunized mice. A significant increase in serum IL-17 and IFN-g levels (p<0.05), as well as expression of CXCL-2, CCL-2, and CXCL-10 in mice immunized with gliadin+CFA, were monitored versus controls. Our findings indicated that the immune responses directed against gliadin peptides might contribute to blood-brain barrier breakdown, extravasation of serum anti-IgG, gliosis, and acute neuronal necrosis in the cortex and cerebellar Purkinje cells. Anti-IgG antibodies may cause extravasation of blood-born anti-gliadin antibodies and selective targeting of Purkinje cells observed in mice immunized with peptide tryptic (pt) -gliadin in CFA. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2590 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2590/1691

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 198 204 Fatemeh Raeesi Nejad Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran AND Department of Immunology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran Mohammad Mahdi Mohammadi Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Mojgan Sanjari Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran Reza Malkpour Afshar Department of Pathology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Elham Jafari Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran 2020 08 20 2020 11 05 Dendritic cells (DCs) play key roles in regulating the immune response using the specialized function of processing and presenting antigens. Prolactin (PRL), a hormone produced by the pituitary gland, participates in DC maturation and function. The present study was aimed to determine the frequencies of peripheral blood DC subpopulations of myeloid DC (MDC) and plasmacytoid DC (PDC) in hyperprolactinemic (HPRL) women compared to normal healthy volunteers. This study was conducted on 70 women, including 35 HPRL patients and 35 matched healthy controls, whose PRL serum levels were in the normal range (lower than 25 ng/mL). Serum thyroid-stimulating hormone (TSH) levels were measured in both groups as an indicator of normal thyroid function. The electrochemiluminescence immunoassay method was applied to measure the serum levels of TSH and PRL. The frequencies of MDC and PDC in the peripheral blood samples of both groups were determined by flow cytometry. The mean serum PRL levels in the HPRL patients and healthy individuals were 46.41±21.96 and 13.75±11.19, respectively (p<0.0001); however TSH levels in both groups were similar and within the normal range (0.4–4.5 mIU/mL) (p=0.2). The frequencies of both MDC and PDC subpopulations in the peripheral blood of HPRL patients were significantly lower than they were in the healthy controls. However, the ratio of MDCs/PDCs in HPRL patients was not significantly different between the two groups (p=0.8). Our study revealed that an increased level of serum PRL may lead to a reduction in the number of MDC and PDC subpopulations. These results could help clarify the complex relationship between the immune system and the neuroendocrine axis and may be of potential use in understanding the pathogenesis of endocrine and immune disorders. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2948 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2948/1687

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 205 220 Fatemeh Khademi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Pantea Mohammadi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Ali Mostafaei Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 2020 03 16 2020 12 22 Despite the unparalleled success of anti-CD20-targeted immunotherapy, the currently available mAbs are not sufficiently efficacious in the treatment of lymphoma. 1F5 is one of a panel of anti-CD20 mAbs that was used in the B-cell lymphoma serotherapy. Despite the efficacy of murine 1F5 mAbs in lymphoma patients, the 1F5 chimeric antibodies with human effector functionality are yet to be approved and widely used in the treatment of lymphoma. In this study, the conversion of 1F5 mAb from mouse IgG2a to human-mouse chimeric IgG1 was achieved and the chimeric antibody was partially characterized. We constructed the 1F5 chimeric mouse-human anti-CD20 antibody genes using an efficient Splicing by overlap extension-polymerase chain reaction (SOE-PCR) technique and cloned the chimeric heavy and light genes in pBudCE4.1mammalian expression vector, followed by purification of the expressed chimeric 1F5 mAbs using affinity chromatography. Our investigation also included the biological properties of purified chimeric antibodies. The generated 1F5 chimeric mAbs mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against Raji and Daudi Burkitt's lymphoma cell lines, which were comparable with rituximab and exhibit superior reduction in cell viability in vitro, compared to rituximab. The current study indicated that the generated chimeric 1F5 mAbs has potential CDC and ADCC activity which was comparable with rituximab whereas it exhibits a superior reduction in cell viability, compared to rituximab. Our work contributes to future studies involving in vivo biological functions and the application of the 1F5 chimeric antibody. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2746 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2746/1692

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 221 232 EN Katayoun Bahman Soufiani Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ali Akbar Pourfathollah Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mahin Nikougoftar Zarif Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Ehsan Arefian Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran 2021 01 15 2021 03 06 Conditioned medium (CM) derived from mesenchymal stem cells (MSCs) contains bioactive molecules including microRNAs (miRs) that could be a potential tool for controlling cancer cells' behavior. Due to the properties of CM, this study assesses the effects of miR-34a related MSC-CM on tumor behavior through the evaluation of migration, invasion, apoptosis, and PDL1 expression in breast cancer cell lines. The miR-34a overexpression vector or scramble control was produced using lentiviral vectors, DNA cloning, and the transfection of the HEK-293T cell line. It was then transduced into human adipose-derived mesenchymal stem cells (hAD-MSCs). MSC-CMs were collected and added onto MDA-MB-231 cell lines. The functional evaluations were performed by transwell, wound healing, and Annexin V/PI methods on the treated MDA-MB-231 cell lines. The PDL1 expression was also assessed by Real-time PCR and western blot. The findings of this study showed that ectopic miR‑34a expression was significantly upregulated in manipulated hASC with miR-34a (p<0.0001). Treatment of MDA-MB-231 cell line with miR-34a-hAD-MSC-CM, scramble-hAD-MSC-CM, or hAD-MSC-CM displayed not only a reduction in the number of migrated or invaded cells (p=0.01) but also an increase in the apoptotic cells in the test group (p=0.02) when compared to the control groups. It also showed down-regulation in the gene (p=0.05) and protein expression levels of PDL1 in the test group. The results of the present study showed that simultaneous application of miR-34a and MSC-CM can be considered as a new method for changing the cancerous microenvironment; and therefore, as a potential strategy in breast cancer therapy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3096 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3096/1701

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 2 2021 04 17 233 243 EN Somayeh Rezaeifard Cancer Immunology and Immunotherapy group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Yuji Heike Laboratory for Joint Research and Development, St. Luke's International Hospital, Tokyo, Japan Jun-Ichi Masuyama New City Osaki Clinic, Tokyo, Japan AND Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan Alireaz Rezvani Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Reza Vojdani Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Nasrollah Erfani Immunology and Immunotherapy group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 2020 04 14 2020 10 31 Natural killer (NK) cell therapy has proven to be a promising approach for the treatment of malignancies. Osaki method for ex-vivo autologous NK cell expansion has been recently introduced in Japan. To start clinical trial phase I at Shiraz University of Medical Sciences in collaboration with the Japanese group, this preclinical setting study aimed to evaluate the proliferative efficacy of the method, the activation status of expanded autologous NK cells, and the likely unwanted contamination of the final cell product. Peripheral blood mononuclear cells (PBMCs) were isolated from 5 healthy individuals' peripheral blood and transferred directly to the specified initial culture bag containing anti-CD52 and anti-CD3 and Interleukin (IL)-2. The cells were cultured for 14-17 days in an incubator, during which the cells received condition media, and underwent several passages into bigger culture bags. All the procedures were carried out in a cleanroom and associated facilities. Before and after activation PBMCs were analyzed for their phenotype and cytotoxic activity; using flow cytometry and cytokine release assay. Our results indicated that NK (CD3-CD16+/-CD56+) cells were expanded 510-fold on average (range 200-1100 fold), and the purity of NK cells per whole lymphocytes exceeded 68%. The expanded cells were highly lytic as indicated by in-vitro cytotoxic assay, with a strong expression of Natural killer group 2 member D (NKG2D) and CD16. The prepared final cell products were negative for HCV, HBV, HIV, mycoplasma, and endotoxin. In the preclinical phase, large numbers of activated and un-contaminated NK cells from healthy individuals' peripheral blood were successfully generated. The method seems to provide ample clean cell product with no contamination and has the potential to be used for NK cell therapy in future clinical trials, suitable to be infused back to the donors in phase I clinical trial. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2792 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2792/1690