Publications by authors named "Mahdi Mahmoudi"

152 Publications

Evaluation of the Ankylosing Spondylitis Transcriptome for Oxidative Phosphorylation Pathway: The Shared Pathway with Neurodegenerative Diseases.

Iran J Allergy Asthma Immunol 2021 Sep 28;20(5):563-573. Epub 2021 Sep 28.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Ankylosing spondylitis (AS) is a systemic inflammatory disorder of joints and entheses. Recent studies have reported an increased prevalence of dementia in AS patients. However, data for exploring the association between dementia and AS remain uncertain. In this study, enriched pathways and differentially expressed genes (DEGs) were identified in whole blood transcription data of AS patients obtained from the gene expression omnibus (GEO) database; using gene set enrichment analysis (GSEA) and differential expression analysis. Four pathways, including oxidative phosphorylation, Alzheimer's, Parkinson's, and Huntington's diseases were significantly enriched in AS patients compared to the controls. We identified 22 common genes among the pathways that showed an increasing trend in AS compared to the controls. Five of them including COX7B, NDUFB3, ATP5PF, UQCRB, and NDUFS4 were the most significant genes which were selected for gene expression analysis; using real-time PCR on RNA contents of peripheral blood mononuclear cells (PBMCs) of AS patients and controls (20 samples from each group). The gene expression analysis indicated considerable overexpression of COX7B (p<0.0001) and ATP5J (p=0.0001) genes in AS patients group in comparison to the control samples. The role of oxidative phosphorylation has previously been established in dementia pathogenesis. Given that AS patients have also a remarkably higher prevalence of dementia than the their healthy counterparts, hence our results may propose that the common pathway of oxidative phosphorylation can be regarded as a possible shared contributing factor in the etiopathogenesis of AS and dementia.
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http://dx.doi.org/10.18502/ijaai.v20i5.7406DOI Listing
September 2021

The role of NK cells in rheumatoid arthritis.

Inflamm Res 2021 Dec 27;70(10-12):1063-1073. Epub 2021 Sep 27.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave., Tehran, Iran.

Objective: Natural killer (NK) cells are part of the innate immune system which not only provides a primary response to pathogenic conditions but can also play an important regulatory role in immune responses. Furthermore, these cells can influence immune responses by affecting other involved cells. Human NK cells can be classified as CD56 and CD56; the former demonstrates mostly cytotoxic effects, while the latter comprises mostly tolerant or regulatory NK cells. These cells participate in the immunopathogenesis of rheumatoid arthritis (RA) and their role remains still unclear.

Methods: We searched PubMed/MEDLINE and Scopus databases to review and analyze relevant literature on the impact of NK cells in the pathogenesis of RA.

Results: Although the percentage of NK cells increases in peripheral blood of RA patients compared to healthy individuals, the cytotoxic function of these cells is impaired. It is demonstrated by reduced "perforin NK cells" and decreased per-cell lytic function. These cytotoxic NK cells may control the pathogenic bone absorptive function of osteoclasts by directly targeting these cells.

Conclusion: Collectively, the evidence collected in the current review emphasizes the possible protective role of CD56 NK cells in the pathogenesis of RA.
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http://dx.doi.org/10.1007/s00011-021-01504-8DOI Listing
December 2021

Dysregulation of ribosome-related genes in ankylosing spondylitis: a systems biology approach and experimental method.

BMC Musculoskelet Disord 2021 Sep 14;22(1):789. Epub 2021 Sep 14.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, PO-BOX: 1411713137, Kargar Ave, Tehran, Iran.

Background: Ankylosing spondylitis (AS) is an autoimmune rheumatic disease. Few candidate gene associations have been reported for AS and the current understanding of its pathogenesis remains still poor. Thus, the exact mechanism of AS is needed to urgently be disclosed. The purpose of this study was to identify candidate genes involving in AS disease.

Methods And Results: GSE25101 publicly available microarray and GSE117769 RNA-seq datasets of AS patients were obtained for bioinformatics analyses. Gene set enrichment analysis showed that in the microarray dataset, the ribosome pathway was significantly up-regulated in AS compared with controls. Furthermore, some ribosomal components demonstrated overexpression in patients in the RNA-seq dataset. To confirm the findings, 20 AS patients and 20 matching controls were selected from the Rheumatology Research Center clinic, Shariati Hospital. PBMCs were separated from whole blood and RNA contents were extracted. Following the results of datasets analysis, the expression level of rRNA5.8S pseudogene, rRNA18S pseudogene, RPL23, RPL7, and RPL17 genes were measured through real-time PCR. Our findings showed dysregulation of rRNA5.8S and rRNA18S pseudogenes, and also the RPL17 gene in patients.

Conclusion: Considering that genes involved in ribosome biogenesis contributed to some AS-associated biological processes as well as diseases that have comorbidities with AS, our results might advance our understanding of the pathological mechanisms of ankylosing spondylitis.
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http://dx.doi.org/10.1186/s12891-021-04662-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442383PMC
September 2021

Association between complement gene polymorphisms and systemic lupus erythematosus: a systematic review and meta-analysis.

Clin Exp Med 2021 Sep 14. Epub 2021 Sep 14.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave., Tehran, Iran.

Complement dysfunction results in impaired ability in clearing apoptotic cell debris that may stimulate autoantibody production in systemic lupus erythematosus (SLE). Herein, we provided a comprehensive search to find and meta-analyze any complement gene polymorphisms associated with SLE. The ITGAM, C1q, and MBL gene polymorphisms were included in this meta-analysis to reveal the exact association with SLE risk. Electronic databases, including Scopus, PubMed, and Google Scholar, were searched to find studies investigating the ITGAM, C1q, and MBL gene polymorphisms and SLE risk in different populations. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were used to analyze the association between ITGAM, C1q, and MBL gene polymorphisms and susceptibility to SLE. According to inclusion criteria, a total of 24 studies, comprising 4 studies for C1QA rs292001, 5 studies for C1QA rs172378, 9 studies for ITGAM rs1143679, 8 studies for MBL rs1800450, 3 studies for MBL2 rs1800451, and 3 studies for MBL2 rs5030737, were included in the final meta-analysis. A significant positive association was found between rs1143679 and SLE risk, while rs1800451 significantly associated with decreased SLE susceptibility. In summary, ITGAM gene rs1143679 SNP and MBL gene rs1800451 SNP were positively and negatively associated with SLE risk, respectively.
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http://dx.doi.org/10.1007/s10238-021-00758-0DOI Listing
September 2021

Monocyte-derived and M1 macrophages from ankylosing spondylitis patients released higher TNF-α and expressed more IL1B in response to BzATP than macrophages from healthy subjects.

Sci Rep 2021 09 8;11(1):17842. Epub 2021 Sep 8.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box: 1411713137, Tehran, Iran.

Macrophages participate in the pathogenesis of ankylosing spondylitis (AS) by producing inflammatory cytokines. Extracellular adenosine triphosphate (eATP), released during cell stress, acts through purinergic receptors (P2XR and P2YR) and induces inflammatory responses. We investigated the effect of 2'(3')-O-(4-benzoyl benzoyl) ATP (BzATP) (a prototypic agonist of P2X7R) on the production of inflammatory cytokines in both monocyte-generated (M2-like) and M1 macrophages from patients and controls. Macrophages were differentiated from isolated periphery-monocytes (n = 14 in each group) by macrophage colony-stimulating factor (M-CSF). Using LPS and IFN-γ, macrophages were skewed toward M1 type and were treated with BzATP. Gene expression and protein release of IL-1β, IL-23, and TNF-α were evaluated by real-time PCR and ELISA methods respectively before and after treatment. BzATP significantly increased the protein release of TNF-α and the expression of TNFA and IL1B in monocyte-generated macrophages. Besides, BzATP treatment significantly upregulated IL1B expression, reduced TNFA and IL23A expression, and TNF-α release in M1 macrophages from both groups. Monocyte-generated and M1 macrophages from AS patients released higher TNF-α and expressed more IL1B in response to the same concentration of BzATP treatment respectively. Based on our results, AS macrophages were more sensitive to BzATP treatment and responded more intensively. Besides, the diverse effects of BzATP on monocyte-derived and M1 macrophages in our study may represent the differed inflammatory properties of these two groups of macrophages in response to eATP in the body.
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http://dx.doi.org/10.1038/s41598-021-96262-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426480PMC
September 2021

Evaluation of TAK-242 (Resatorvid) Effects on Inflammatory Status of Fibroblast-like Synoviocytes in Rheumatoid Arthritis and Trauma Patients.

Iran J Allergy Asthma Immunol 2021 Aug 7;20(4):453-464. Epub 2021 Aug 7.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

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.
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August 2021

Co-expression Network Analysis Reveals Key Genes Related to Ankylosing spondylitis Arthritis Disease: Computational and Experimental Validation.

Iran J Biotechnol 2021 Jan 1;19(1):e2630. Epub 2021 Jan 1.

Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.

Background: Ankylosing spondylitis (AS) is a type of arthritis which can cause inflammation in the vertebrae and joints between the spine and pelvis. However, our understanding of the exact genetic mechanisms of AS is still far from being clear.

Objective: To study and find the mechanisms and possible biomarkers related to AS by surveying inter-gene correlations of networks.

Materials And Methods: A weighted gene co-expression network was constructed among genes identified by microarray analysis, gene co-expression network analysis, and network clustering. Then receiver operating characteristic (ROC) curves were conducted to identify a significant module with the genes implicated in the AS pathogenesis. Real-time PCR was performed to validate the results of microarray analysis.

Results: In the significant module obtained from the network analysis there were eight AS related genes (LSM3, MRPS11, , , , , and ) which have been reported in previous studies as hub genes. Further, in this module, eight significant enriched pathways were found with adjusted p-values < 0.001 consisting of oxidative phosphorylation, ribosome, nonalcoholic fatty liver disease, Alzheimer's, Huntington's, and Parkinson's diseases, spliceosome, and cardiac muscle contraction pathways which have been linked to AS. Furthermore, we identified nine AS related genes (, , , , , , , and ) in these pathways which can play essential roles in controlling mitochondrial activity and pathogenesis of autoimmune diseases. Real-time PCR results showed that three genes including , , and in AS patients were significantly differentially expressed compared with normal controls.

Conclusions: The results of the present study may contribute to understanding of AS molecular pathogenesis, thereby aiding the early prognosis, diagnosis, and effective therapies of the disease.
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http://dx.doi.org/10.30498/IJB.2021.2630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217537PMC
January 2021

Downregulation of ITM2A Gene Expression in Macrophages of Patients with Ankylosing Spondylitis.

Int Arch Allergy Immunol 2021;182(11):1113-1121. Epub 2021 Jun 23.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Ankylosing spondylitis (AS) is a rheumatic disorder that is mostly determined by genetic and environmental factors. Given the known importance of macrophage in AS pathogenesis, we investigated the transcriptional profile of macrophage cells in the disease.

Methods And Results: Two approaches of differential expression and subsequently, weighted gene co-expression network analysis was utilized to analyze a publicly available microarray dataset of macrophages. Integral membrane protein 2A (ITM2A) was among the most significant genes with a decreased trend in the common results of both methods. In order to confirm the finding, the expression of ITM2A was evaluated in monocyte-derived (M2-like) and M1 macrophages obtained from 14 AS patients and 14 controls. Macrophages were differentiated from whole-blood separated monocytes by 7 days incubating with macrophage colony-stimulating factor and then macrophages specific markers were verified with the flow cytometer. M1 polarization was induced by IFN-γ and lipopolysaccharide. Finally, relative gene expression analysis by real-time polymerase chain reaction revealed a significant downregulation of the ITM2A gene in both M2 like and M1 macrophages of the AS group compared to the control.

Conclusion: Since ITM2A plays a critical role in osteo- and chondrogenic cellular differentiation, our finding may provide new insights into AS pathogenesis.
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http://dx.doi.org/10.1159/000516179DOI Listing
November 2021

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

Ann Rheum Dis 2021 09 20;80(9):1168-1174. Epub 2021 Apr 20.

Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.

Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), and sacroiliac MRI.

Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for these values were 51.9% and 97.9%, respectively.

Conclusions: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.
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http://dx.doi.org/10.1136/annrheumdis-2020-219446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364478PMC
September 2021

Role of Fibroblast Activation Protein Alpha in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Iran J Allergy Asthma Immunol 2021 Jun 6;20(3):338-349. Epub 2021 Jun 6.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.
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http://dx.doi.org/10.18502/ijaai.v20i3.6335DOI Listing
June 2021

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis.

J Neuromuscul Dis 2021 ;8(5):827-829

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.
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http://dx.doi.org/10.3233/JND-210700DOI Listing
January 2021

The p53 status in rheumatoid arthritis with focus on fibroblast-like synoviocytes.

Immunol Res 2021 06 13;69(3):225-238. Epub 2021 May 13.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, PO-BOX: 1411713137, Tehran, Iran.

P53 is a transcription factor that regulates many signaling pathways like apoptosis, cell cycle, DNA repair, and cellular stress responses. P53 is involved in inflammatory responses through the regulation of inflammatory signaling pathways, induction of cytokines, and matrix metalloproteinase expression. Also, p53 regulates immune responses through modulating Toll-like receptors expression and innate and adaptive immune cell differentiation and maturation. P53 is a modulator of the apoptosis and proliferation processes through regulating multiple anti and pro-apoptotic genes. Rheumatoid arthritis (RA) is categorized as an invasive inflammatory autoimmune disease with irreversible deformity of joints and bone resorption. Different immune and non-immune cells contribute to RA pathogenesis. Fibroblast-like synoviocytes (FLSs) have been recently introduced as a key player in the pathogenesis of RA. These cells in RA synovium produce inflammatory cytokines and matrix metalloproteinases which results in synovitis and joint destruction. Besides, hyper proliferation and apoptosis resistance of FLSs lead to synovial hyperplasia and bone and cartilage destruction. Given the critical role of p53 in inflammation, apoptosis, and cell proliferation, lack of p53 function (due to mutation or low expression) exerts a prominent role for this gene in the pathogenesis of RA. This review focuses on the role of p53 in different mechanisms and cells (specially FLSs) that involved in RA pathogenesis.
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http://dx.doi.org/10.1007/s12026-021-09202-7DOI Listing
June 2021

Reply: Is high-dose glucocorticoid beneficial in COVID-19?

Eur Respir J 2021 04 15;57(4). Epub 2021 Apr 15.

Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

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http://dx.doi.org/10.1183/13993003.00324-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898159PMC
April 2021

Transformation of fibroblast-like synoviocytes in rheumatoid arthritis; from a friend to foe.

Auto Immun Highlights 2021 Feb 5;12(1). Epub 2021 Feb 5.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.
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http://dx.doi.org/10.1186/s13317-020-00145-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863458PMC
February 2021

Investigating the possible association between NLRP3 gene polymorphisms and myasthenia gravis.

Muscle Nerve 2021 05 18;63(5):730-736. Epub 2021 Feb 18.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: In this case-control study, we investigated the association between nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) single-nucleotide polymorphisms (SNPs) rs10754558, rs3806265, rs4612666, and rs35829419 and myasthenia gravis (MG).

Methods: Samples from MG patients were selected from a previous study conducted in our neuromuscular clinic, which investigated the association between human leukocyte antigen (HLA) class II genes and MG. Genetic data of controls were also available from another study. The NLRP3 SNPs genotyping was performed using the TaqMan method.

Results: A total of 93 blood samples from eligible Iranian patients with MG and 56 samples from healthy controls were obtained. The NLRP3 rs3806265 "C" allele was significantly more frequent in MG patients (P < .001; odd ratio [OR] = 2.33, 95% confidence interval [CI]: 1.4-4.0) than controls. The "CC" genotype of this SNP was found in 18.27% of patients, but none of the controls (P < .001). The distribution of other SNPs was similar between the groups.

Discussion: These preliminary results suggest that there might be some associations between the NLRP3 gene polymorphism and MG.
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http://dx.doi.org/10.1002/mus.27193DOI Listing
May 2021

Association of gene polymorphisms with Type 1 Diabetes: a meta-analysis.

J Diabetes Metab Disord 2020 Dec 9;19(2):1777-1786. Epub 2020 Jul 9.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, PO-BOX: 1411713137, Kargar Ave., Tehran, Iran.

Purpose: Type 1 Diabetes (T1D) is a T cell-mediated disease, in which autoimmune destruction of insulin-producing β-cells in pancreatic islets occurs. In recent decades, the role of Killer cell immunoglobulin-like receptor () gene polymorphisms in susceptibility to T1D has been demonstrated in an increased number of studies. Nonetheless, inconsistency has been observed in the results of performed association studies. To comprehensively clarify the association among gene polymorphisms and the risk of T1D, this meta-analysis on the previously published association studies was carried out via incorporating multiple research.

Methods: No publication has been recorded from Nov 2017 until July 2020 about the KIR genes and T1D. The PubMed/MEDLINE and Scopus databases were systematically searched up to November 2017 to identify investigations on the impact of the polymorphisms of genes on susceptibility to T1D. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated. Funnel plot and Egger test were used to assess the publication bias. Thirteen qualified published case-control articles were found for evaluation in this meta-analysis.

Results: Our results show statistical significance between the genetic variations in the (OR = 0.42, 95% CI = 0.23-0.77;  = 0.005), (OR = 1.15, 95% CI = 1.00-1.32;  = 0.048), and (OR = 0.86, 95% CI = 0.75-0.98;  = 0.03) with susceptibility to T1D.

Conclusions: This meta-analysis study provides reliable evidence that gene polymorphisms may contribute to T1D risk. and genes might be considered as a protective factor for T1D, while seemed to be a susceptibility factor.
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http://dx.doi.org/10.1007/s40200-020-00569-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843782PMC
December 2020

Distinctive Expression of Bone Metabolism-related Genes between PBMCs from Condylar Hyperplasia, Rheumatoid Arthritis, and Ankylosing Spondylitis Patients.

Iran J Allergy Asthma Immunol 2020 Oct 18;19(5):539-544. Epub 2020 Oct 18.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran AND Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Bone morphogenetic proteins (BMPs) and wingless (Wnt) signaling molecules and their antagonists, such as sclerostin and noggin, have been identified to have different effects on bone metabolism. This research intended to evaluate the transcript levels of CTNNB1 (catenin beta 1protein), SOST (sclerostin protein), BMP4 (Bone Morphogenetic Protein 4 protein), and NOG (noggin protein) bone metabolism-related genes in peripheral blood mononuclear cells (PBMCs) from condylar hyperplasia (CH) patients in comparison to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy individuals. PBMCs were separated from blood samples of 10 patients with CH, AS, RA, and 10 healthy controls. SYBR Green real-time polymerase chain reaction (PCR) was used for quantitative analysis of CTNNB1, SOST, BMP4, and NOG messenger RNAs (mRNAs). The expression of CTNNB1 was significantly upregulated in CH and AS patients compared with healthy individuals and RA patients. The difference of SOST expression was not significant between all groups. The BMP4 expression was significantly downregulated in AS, CH, and RA patients compared with healthy controls. The NOG expression was downregulated in RA, AS, and CH groups, however, it was only significant in CH and RA patients compared with controls.CH and AS patients were distinguished from RA by the upregulatedCTNNB1 expression. These results demonstrated that CTNNB1, BMP4, and NOG, but not SOST, may contribute to the pathogenesis of CH, AS, and RA.
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http://dx.doi.org/10.18502/ijaai.v19i5.4471DOI Listing
October 2020

Evaluation of autoantibodies against vimentin and α-enolase in rheumatoid arthritis patients.

Reumatologia 2020 23;58(6):350-356. Epub 2020 Dec 23.

Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.

Introduction: Rheumatoid arthritis (RA) is categorized as an autoimmune disease with a frequency of 0.2-1% worldwide. It is reported that various autoantibodies are produced in the RA population, particularly against citrullinated peptides. Among various candidate markers for RA diagnosis, the citrullinated proteins have the highest specificity and sensitivity for both diagnosis and prognosis of RA. Anti-mutated citrullinated vimentin and α-enolase constitute a new class of autoantibodies for early detection of RA.

Material And Methods: 45 serum samples and 19 synovial fluid (SF) specimens collected from RA patients were considered for American College of Rheumatology criteria and 20 serum samples and 10 SF specimens were provided from healthy subjects as a control group. To assess the quantity of anti-citrullinated protein antibodies (ACPA), anti-mutated citrullinated vimentin (MCV) and anti-α-enolase in the serum and SF of RA patients were determined by the enzyme-linked immunosorbent assay (ELISA) method. For the evaluation of disease activity and joint destruction, we used the Disease Activity Score of 28 joints based on erythrocyte sedimentation rate (ESR) Disease Activity Score 28 (DAS28). Furthermore, to measure the molecular weight of vimentin and α-enolase, electrophoresis on 10% SDS-PAGE was performed as described before.

Results: The anti-α-enolase level among serum samples from RA patients was significantly higher than in healthy subjects (4.49 ±0.20 ng/ml vs. 0.76 ±0.12 ng/ml) ( < 0.001). There was a direct relation between α-enolase quantity and (rheumatoid factor) RF and C-reactive protein (CRP) levels. The mean ESR value in positive and negative ACPA patients was 38.2 ±22.6 mm/h and 9.2 ±5.8 mm/h respectively ( < 0.0001). The mean DAS28-ESR was 3.3. The level of anti-MCV in the serum of RA patients (244.6 ±53.3 U/ml) was higher than in serum of the healthy group (148.73 ±71.8) ( < 0.0001). The level of anti-MCV in the SF of patients was 687.5 ±148.4 U/ml.

Conclusions: In conclusion, both autoantibodies against MCV and α-enolase are two important markers that increase in serum and SF of RA patients and are specific for diagnosis of RA disease.
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http://dx.doi.org/10.5114/reum.2020.101276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792540PMC
December 2020

Escape from X chromosome inactivation and female bias of autoimmune diseases.

Mol Med 2020 12 9;26(1):127. Epub 2020 Dec 9.

Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Generally, autoimmune diseases are more prevalent in females than males. Various predisposing factors, including female sex hormones, X chromosome genes, and the microbiome have been implicated in the female bias of autoimmune diseases. During embryogenesis, one of the X chromosomes in the females is transcriptionally inactivated, in a process called X chromosome inactivation (XCI). This equalizes the impact of two X chromosomes in the females. However, some genes escape from XCI, providing a basis for the dual expression dosage of the given gene in the females. In the present review, the contribution of the escape genes to the female bias of autoimmune diseases will be discussed.
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http://dx.doi.org/10.1186/s10020-020-00256-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727198PMC
December 2020

Graves' disease: introducing new genetic and epigenetic contributors.

J Mol Endocrinol 2021 02;66(2):R33-R55

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Autoimmune thyroid disease (AITD) accounts for 90% of all thyroid diseases and affects 2-5% of the population with remarkable familial clustering. Among AITDs, Graves' disease (GD) is a complex disease affecting thyroid function. Over the last two decades, case-control studies using cutting-edge gene sequencing techniques have detected various susceptible loci that may predispose individuals to GD. It has been presumed that all likely associated genes, variants, and polymorphisms might be responsible for 75-80% of the heritability of GD. As a result, there are implications concerning the potential contribution of environmental and epigenetic factors in the pathogenesis of GD, including its initiation, progression, and development. Numerous review studies have summarized the contribution of genetic factors in GD until now, but there are still some key questions and notions that have not been discussed concerning the interplay of genetic, epigenetic, and immunological factors. With this in mind, this review discusses some newly-identified loci and their potential roles in the pathogenicity of GD. This may lead to the identification of new, promising therapeutic targets. Here, we emphasized principles, listed all the reported disease-associated genes and polymorphisms, and also summarized the current understanding of the epigenetic basis of GD.
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http://dx.doi.org/10.1530/JME-20-0078DOI Listing
February 2021

A comprehensive overview on the genetics of Behçet's disease.

Int Rev Immunol 2020 Dec 1:1-64. Epub 2020 Dec 1.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as , , , and have been found as independent risk factors for BD, whereas and are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including , , , , , , , , and . Also, several rare nonsynonymous variants in , , , and genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.
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http://dx.doi.org/10.1080/08830185.2020.1851372DOI Listing
December 2020

Functional Analysis of S2486G Mutation and its Contribution to Pathogenesis of Ankylosing Spondylitis.

Arch Iran Med 2020 10 1;23(10):688-696. Epub 2020 Oct 1.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: Ankylosing spondylitis (AS; OMIM:106300) is a common complex inflammatory disease; in a previous study, we introduced a novel mutation in the gene (OMIM: 600514) which was associated with AS. This study is designed to investigate the potential effect of S2486G mutation on reelin secretion; additionally, we objected to evaluate the phospholipase A2 () gene (OMIM: 601690) expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration as the downstream gene and the encoded protein.

Methods: The impact of the S2486G on reelin protein secretion was investigated in CHO-K1 and HEK-293T cells by constructing wild-type and mutant plasmids. Besides, the possible effect of the mutation on expression and concentration of and PAF-AH in THP1 cells was assessed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The study was performed at Tarbiat Modares University, Tehran, Iran, from 2016 to 2018.

Results: Our results showed that S2486G not only causes a significant reduction in reelin secretion in both HEK-293T and CHO-K1 cells, but also it leads to a significant reduction in gene expression ( value < 0.001) and protein level of PAF-AH in THP-1 cells ( value < 0.003).

Conclusion: The S2486G mutation in can alter inflammatory and, to some extent, osteogenesis pathways mediated by reduced secretion of reelin and also reduced expression of the gene.
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http://dx.doi.org/10.34172/aim.2020.87DOI Listing
October 2020

Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

J Immunol Res 2020 19;2020:4873648. Epub 2020 Sep 19.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Genetic studies have illustrated that () genes could participate in various autoimmune disorders. We aimed to clarify the role of genes, ligands, HLA-KIR interactions, and their genotypes in inflammatory bowel disease (IBD) susceptibility. The study population was composed of 183 IBD subjects, comprising 100 ulcerative colitis (UC) patients, 83 Crohn's disease (CD) patients, and 274 healthy subjects. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to evaluate the absence or presence of the 15 genes, 5 class I ligands, and 2 pseudogenes. We did not find any significant difference in allele frequency of and pseudogenes between IBD patients and healthy controls. In the case of genes, there was a significant difference in frequency between UC patients and healthy controls ( = 0.03, OR = 0.06, 95%CI = 0.008-0.4). Furthermore, we found a significant difference in frequency between CD patients and healthy controls ( = 0.04, OR = 0.49, 95% CI = 0.3-0.8). In the full-array combination of genes, there was no significant frequency difference between UC patients and healthy controls, while two KIR genotypes showed a significant susceptible association with CD. Our data do not support a strong role of NK cells in IBD susceptibility, but it does not rule out a role for KIR variability in IBD patients. However, there are some protective associations such as Bw4 alleles; these associations may be due to the interaction of the alleles to TCRs rather than KIRs.
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http://dx.doi.org/10.1155/2020/4873648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520679PMC
July 2021

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.

Eur Respir J 2020 12 24;56(6). Epub 2020 Dec 24.

Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Introduction: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients.

Methods: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population.

Results: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study.

Conclusions: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.
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http://dx.doi.org/10.1183/13993003.02808-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758541PMC
December 2020

The effect of black barberry hydroalcoholic extract on immune mediators in patients with active rheumatoid arthritis: A randomized, double-blind, controlled clinical trial.

Phytother Res 2021 Feb 10;35(2):1062-1068. Epub 2020 Sep 10.

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production.
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http://dx.doi.org/10.1002/ptr.6874DOI Listing
February 2021

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing.

J Clin Lab Anal 2020 Dec 30;34(12):e23544. Epub 2020 Aug 30.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Teheran, Iran.

Background: The extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL).

Methods: After excluding mutations in the most common ARNSHL gene, GJB2, by Sanger sequencing, genetic screening for a panel of genes responsible for hereditary hearing impairment performed in 9 individuals with ARNSHL from unrelated Iranian consanguineous pedigrees.

Results: One compound heterozygote and eight homozygote variants, of which five are novel, were identified: CDH23:p.(Glu1970Lys), and p.(Ala1072Asp), GIPC3:p.(Asn82Ser), and (p.Thr41Lys), MYO7A:p.[Phe456Phe]; p.[Met708Val], and p.(Gly163Arg), TECTA:p.(Leu17Leufs*19), OTOF:c.1392+1G>A, and TRIOBP:p.(Arg1068*). Sanger sequencing confirmed the segregation of the variants with the disease in each family.

Conclusion: Finding more variants and expanding the spectrum of hearing impairment mutations can increase the diagnostic value of molecular testing in the screening of patients and can improve counseling to minimize the risk of having affected children for at risk couples.
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http://dx.doi.org/10.1002/jcla.23544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755797PMC
December 2020

Copy number variation of IL17RA gene and its association with the ankylosing spondylitis risk in Iranian patients: a case-control study.

BMC Med Genet 2020 07 10;21(1):147. Epub 2020 Jul 10.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Ankylosing spondylitis (AS) is considered as a subtype of spondyloarthritis (SpA) that mainly leads to fatigue, stiffness, spinal ankylosis, and impaired physical functions with reduced quality of life. Interleukin (IL)-17A provokes additional inflammatory mediators and recruits immune cells to the inflamed site. IL17 expression increased in various inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, crohn's disease, and ankylosing spondylitis. The current study aimed to evaluate the association of IL17RA copy number changes with the susceptibility to AS and their correlation to IL17RA expression in Iranian population.

Methods: IL17RA copy number genotyping assessments were carried out in 455 AS patients and 450 healthy controls, using custom TaqMan CNV assays. TaqMan primers and probe were located in Chr.22:17109553 based on pre-designed IL17RA Copy Number Assay ID, Hs02339506_cn. mRNA expression of IL17RA was also measured by SYBR Green real-time polymerase chain reaction (PCR).

Results: A IL17RA copy number loss (< 2) was associated with AS compared to 2 copies as reference (OR:2.18, 95% CI: (1.38-3.44), P-value < 0.001) and increased the risk of AS. IL17RA mRNA expression showed a significant increase in peripheral blood mononuclear cells (PBMCs) of all AS individuals than controls. The mRNA expression level of 2 copies was significantly higher in AS patients.

Conclusions: Our findings revealed that a low copy number of IL17RA might confer a susceptibility risk to AS. However, it is probably not directly involved in the regulation of IL17RA mRNA expression. Epigenetic mechanisms like DNA methylation, post-transcriptional, and -translational modifications that regulate the expression of the genes may contribute in upregulation of IL17RA mRNA expression in the loss of gene copy number condition.
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http://dx.doi.org/10.1186/s12881-020-01078-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350761PMC
July 2020

Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers.

Immunol Invest 2021 Aug 29;50(6):646-661. Epub 2020 Jun 29.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Dendritic cells (DCs) are considered as a subset of mononuclear phagocytes that composed of multiple subsets with distinct phenotypic features. DCs play crucial roles in the initiation and modulation of immune responses to both allo- and auto-antigens during pathogenic settings, encompassing infectious diseases, cancer, autoimmunity, transplantation, as well as vaccination. DCs play a role in preventing autoimmunity via inducing tolerance to self-antigens. This review focus on the most common subsets of DCs in human. Owing to the low frequencies of DC cells in blood and tissues and also the lack of specific DC markers, studies of DCs have been greatly hindered. Human DCs arise by a dedicated pathway of lympho-myeloid hematopoiesis and give rise into specialized subtypes under the influence of transcription factors that are specific for each linage. In humans, the classification of DCs has been generally separated into the blood and cutaneous subsets, mainly because these parts are more comfortable to examine in humans.
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http://dx.doi.org/10.1080/08820139.2020.1783289DOI Listing
August 2021

IL-27 and autoimmune rheumatologic diseases: The good, the bad, and the ugly.

Int Immunopharmacol 2020 Jul 29;84:106538. Epub 2020 Apr 29.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials.
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http://dx.doi.org/10.1016/j.intimp.2020.106538DOI Listing
July 2020

The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: A randomized controlled trial.

Med J Islam Repub Iran 2019 27;33:154. Epub 2019 Dec 27.

Departments of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory disease that affects the joints and consequently leads to the destruction of cartilage and bone lesions. Traditionally, ginger has been consumed in treatment of osteoarthritis, joint and muscle pain, neurological diseases, and inflammation of gums, tooth pain, asthma, stroke, diabetes, and constipation. The aim of this study was to determine the effect of ginger on some immunological and inflammatory markers in patients with rheumatoid arthritis. In this study, which was performed during 2013-2016, 66 patients with active rheumatoid arthritis who referred to the rheumatology clinic at Shariati hospital were en-rolled. Patients were randomly divided into 2 groups: one group consumed 1.5 gr ginger per day, and the other group took roasted wheat flour (placebo), respectively. To determine the effect of confounding factors on the findings of the study, questionnaires for nutrient intake, physical activity, and medication were filled, and BMI was measured. For each participant, at the beginning and end of the study, Serum hs-CRP and mRNA levels of IL-1β, IL-2 and TNF-α were determined by ELISA and Quantitative Real Time PCR, respectively. Statistical analysis was performed using SPSS software. Significance level was set at p<0.05. Results of the study showed ginger powder supplementation caused a significant decline in CRP (p=0.050) and IL-1β mRNA level (p=0.021). TNFα mRNA levels reduced in ginger group compared to placebo groupalthough the difference was not significant between the 2 groups (p=0.093). Ginger had no effects on IL2 gene expression. This study showed that ginger reduces inflammatory factors hs-CRP and IL-1β gene expression in patients with active RA and it seems that ginger can improve the inflam-mation in the patients.
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http://dx.doi.org/10.34171/mjiri.33.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137811PMC
December 2019
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