Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 04 27 235 244 Hami Ashraf Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran Farid Kosari Department of Pathology and Laboratory Medicine, Tehran University of Medical Sciences, Tehran, Iran 2023 08 29 2024 02 05 Graft-versus-host disease (GvHD), a frequent and severe complication following allogeneic hematopoietic stem cell transplantation, presents substantial morbidity and mortality risks. The crucial role of histopathological examination in diagnosing and grading GvHD, particularly within animal models, is pivotal for elucidating disease mechanisms and assessing emerging therapies. This systematic review aims to critically evaluate the various grading systems for GvHD in animal models, emphasizing histopathological characteristics. In this endeavor, we meticulously examined original research articles sourced from PubMed, Scopus, Web of Science, and Google Scholar. Our findings reveal a diverse array of grading systems, each differing in the tissues examined, criteria evaluated, severity scoring scales, and the granularity of the information provided. Predominantly, skin, liver, and gut tissues are assessed, though some systems also incorporate lung and thymus evaluations. This review will delve into the alignment between clinical and histological grading in animal models of GvHD, also casting light on prospective advancements and the impact of technological progress. In conclusion, our analysis underscores the imperative need for uniform criteria and consistent application of grading systems. Such standardization is essential to foster comparability across studies and enhance the translation of preclinical discoveries into clinical applications. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3907 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3907/2070

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 245 256 Emel Atayik Department of Allergy and Clinical Immunology, Konya City Hospital, University of Health Sciences, Konya, Turkey Gokhan Aytekin Department of Allergy and Clinical Immunology, Konya City Hospital, University of Health Sciences, Konya, Turkey İsa Aydin Department of ENT, University of Health Sciences, Konya City Hospital, Konya, Turkey Etem Omeroglu Department of Pathology, Konya City Hospital, University of Health Sciences, Konya, Turkey 2023 01 22 2024 01 29 Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=−0.485), between ∆ACT and ∆NP scores (r=−0.469), and ∆ACT and ∆LM scores (r=−0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3752 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3752/2071

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 257 271 EN Hamid Nickho Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Reza Falak Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Fereshteh Rezagholizadeh Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran AND Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Majid Khoshmirsafa Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Taghi Joghataei Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran AND Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran AND Department of Innovation in Medical Education (DIME), Faculty of Medicine, University of Ottawa, Ottawa, Canada Shabnam Mollazadeh Ghomi Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Board for Transplantation and Cell-Based Therapeutics (ImmunoTACT), Universal Scientific Education and Research Network (USERN), Tehran, Iran Elaheh Safari Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 2023 10 23 2024 01 02 V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry. Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation.  Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival. In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3935 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3935/2072

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 272 287 Nasrin Noshadi Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran AND Department of Biology, Fars Science and Research Branch, Islamic Azad University, Marvdasht, Iran Ramin Yaghoubi Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Afsoon afshari Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Mohsen Forouzanfar Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran Saeede Soleimanian Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2024 01 03 2024 03 28 Reactivation of Polyomavirus BK (BKPyV) is related to reduction of T cells response in kidney transplant recipients (KTRs). Here, we examined the differentiation of CD4+ T cells subsets in response to BKPyV KTRs, using the BKPyV VP1 (viral capsid protein 1) as a stimulator. We categorized our samples into three distinct groups: 1. Reactive BKPyV (BKPyV+), 2. non-reactive (BKPyV-) KTRs and 3. Healthy controls. BKPyV- KTRs and healthy controls stimulated with VP1 and BKPyV+ unstimulated with VP1. The human CD4+ T cells was stimulation with VP1-Ag. The proportion of CD4+ T lymphocytes and their various subsets, including naive T cells, central memory T cells (TCM), and effector memory T cells (TEM) was measured using flowcytometry. BKPyV- KTRs VP1+ indicated significantly lower TCM CD4+ T cells in contrast with both BKPyV+ KTRs VP1-, and healthy controls VP1+. This indicates that VP1 stimulation may reduce TCM cell levels in these patients. The percentage of TEM in the BKPyV- KTRs VP1+ group was significantly less prevalent than the BKPyV+ KTRs VP1- group. The percentage of TEM cells in BKPyV+ KTRs VP1- was significantly lower than the healthy controls VP1+. Stimulation with VP1 protein significantly increased the frequency of cytotoxic CD4+ T cells in BKPyV- KTRs VP1+ compared to BKPyV+ KTRs VP1-. The present research has shown that the VP1 stimulation of CD4+ T cells can induce cytotoxic CD4+ T cells responses that may help overcome BKPyV infection in KTRs. However, VP1 stimulation may also differentially affect TCM and TEM CD4+ T cells subsets. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3984 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3984/2073

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 288 298 EN Ava Misaghian Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran Ata A Ghadiri Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran AND Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Ali Asadirad Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran AND Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Sareh Amirzadeh Department of Infertility, Infertility Research and Treatment Center of ACECR, Ahvaz, Iran Afshin Amari Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran AND Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2024 01 11 2024 04 17 Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton’s Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3996 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3996/2074

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 299 310 Yaqi Wang Medical School of Hebei University, Baoding, China AND Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases, Baoding, China Min Zhang Medical School of Hebei University, Baoding, China AND Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases, Baoding, China Shengde Chen Medical School of Hebei University, Baoding, China AND Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases, Baoding, China Zheng Li Affiliated Hospital of Hebei University, Baoding, China Ming Meng Medical School of Hebei University, Baoding, China AND Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases, Baoding, China 2023 11 27 2024 02 16 Rheumatoid arthritis (RA) is a type of autoimmune disease that results in immune disorder and excessive inflammatory response due to a reduction of self-tolerance. Invariant natural killer T (iNKT) cells can effectively alleviate clinical symptoms and hyper-inflammation in RA, but their mechanism of action is not well-defined. This study aims to investigate the mechanism of iNKT cell therapy for RA. We established a DBA/1 mouse model for RA and treated it with specific iNKT cells. A cytometric bead array was used to measure the amounts of cytokines in the serum. Flow cytometry was then employed to identify different subsets of helper T cells (Th), the frequency of conventional dendritic cells (cDC), the expression of CD80, CD86, programmed cell death ligand 1 (PD-L1), and PD-L2 on cDC surfaces, and associated pathway proteins. iNKT cell treatment reduced Th1/Th2 and Th17/ regulatory T (Treg) cell ratios while increasing interleukin-4 (IL-4) and Zakaria Bameri Infectious Disease and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran 2024 03 12 2024 05 28 Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID‐19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the progression of COVID-19 and their correlation with clinical characteristics. Next‐generation sequencing with high throughput was used to identify mtDNA mutations in 30 COVID-19 patients compared to 20 healthy controls. The potential impact of identified mutations on protein structure and stability was predicted using bioinformatic tools. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of mtDNA-encoded genes involved in oxidative phosphorylation in COVID-19 patients and healthy controls. Correlations between gene expression levels, clinical parameters, including leukocyte, lymphocyte, neutrophil, and platelet count, as well as creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and blood urea nitrogen (BUN) levels, and disease severity were analyzed. We found 8 different mtDNA mutations in ND1, ND5, CO3, ATP6, and CYB genes, which were predicted to alter amino acids and decrease protein stability. Two missense unique mutations, C9555T in CO3 and A12418T in ND5 were identified and correlated with Complexes I and IV, respectively. This downregulation was correlated with age, elevated levels of leukocytes, lymphocytes, neutrophils, platelets, creatinine, ALT, AST, and BUN, as well as disease severity. These findings suggest that mtDNA mutations and altered expression of oxidative phosphorylation genes contribute to mitochondrial dysfunction in COVID-19. Targeting mitochondrial dysfunction may represent a promising therapeutic strategy for COVID-19 treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4051 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4051/2091

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 4 2024 07 27 393 402 Azam Kia Basic Science School, East Branch, Payame Noor University, Tehran, Iran Vahideh Hajhasan 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 Azam Samei Allied Medical Science Faculty, Kashan University of Medical Science School, Kashan, Iran Sadeq Azimzadeh Jamalkandi Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Shahram Parvin Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ali Saffaie Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran Pedram Basirjafar Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Jafar Salimian Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Azam Samei Allied Medical Science Faculty, Kashan University of Medical Science School, Kashan, Iran 2023 12 11 2024 03 03 The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment. The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC). The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-κB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold). CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3977 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3977/2083

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 4 2024 07 27 403 411 Qiang Wang Department of Cardiothoracic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China Mao Deng Department of Cardiothoracic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China Bo Wang Department of Cardiothoracic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China 2023 07 19 2024 02 09 Peripheral benign lung tumors are often asymptomatic and incidentally detected on chest radiographs. Surgical intervention is recommended when feasible. Single-port thoracoscopic resection has emerged as a promising technique for treating various chest diseases, including lung tumors. This study aimed to assess the clinical efficacy of single-port thoracoscopic resection for benign lung tumors and its impact on respiratory function and inflammatory factors. A total of 128 eligible patients diagnosed with benign lung tumors were randomly assigned to either the observation group (undergoing single-port thoracoscopic resection) or the control group (undergoing conventional thoracic surgery). Surgical outcomes, complications, pulmonary and respiratory function, and inflammatory factors were compared between the two groups. The observation group showed significantly lower intraoperative bleeding, shorter hospitalization time, and lower complication rates compared to the control group. Patients in the observation group exhibited higher vital capacity (VC), forced vital capacity (FVC), and total lung capacity (TLC) levels at 1/2 week and 1 month after surgery. Additionally, forced expiratory volume in one second (FEV1) and maximum ventilation volume per minute (MVV) levels were higher in the observation group post-surgery, with a lower Borg score. Levels of C-reactive protein (CRP), precalcitonin (PCT), and tumor necrosis factor (TNF-α) were lower in the observation group post-surgery. Single-port thoracoscopic resection demonstrates favorable clinical efficacy for treating benign lung tumors, reducing bleeding, and shortening hospital stays. Furthermore, it improves lung and respiratory function while reducing inflammatory factors. This technique is safe, effective, and holds promise for wider application in managing benign lung tumors. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3878 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3878/2099

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 4 2024 07 27 412 421 Shabnam Akhgar Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran Shamsi Noorpisheh Ghadimi Department of Parasitology and Mycology, School of Allied Medicine Sciences, Fasa University of Medical Sciences, Fasa, Iran Ibrahim Farhani Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran Abdolmajid Ghasemian Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran Shirin Mahmoodi Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran Mehdi mardkhoshnood Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran Ali Zarenezhad Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran 2023 12 06 2024 04 07 As the most common cause of bacillary dysentery or shigellosis, Shigella sonnei (S nonnei) has spread throughout the world. Invasion of the colorectal epithelial cells by this facultative intracellular bacterium occurs via various virulence factors. The increase in the resistance rate highlights the need for novel interventions, particularly increasing the urgency of the development of Shigella vaccines that may offer an effective solution. A multiepitope protein vaccine (MEPV) construct previously designed using bioinformatics tools against Shigella species, was applied in vivo in BALB/C mice. The designed vaccine construct was expressed in a bacterial host, purified, and finally confirmed by Western blot analysis. The immunogenicity of the purified MEPV was assessed against S sonnei via intranasal and subcutaneous administration routes, followed by evaluating its protective efficiency. We observed that interferon-gamma, interleukin-4, and immunoglobulin G levels were increased in all experimental groups. Therefore, The MEPV effectively protected the mice against S sonnei. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3966 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3966/2085

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 4 2024 07 27 422 436 Danyal Imani Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Tannaz Bahadori Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mohammad Ali Judaki Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Maryam Mobini Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mahmood Jeddi-Tehrani Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran Mohammad Mehdi Amiri Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Fazel Shokri