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Objectives: SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study., Methods: This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method., Results: The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [P = 2.10 × 10-24, odds ratio (OR) = 3.14] and DPB1*13: 01 (P = 5.37 × 10-14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 (P = 4.90 × 10-11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 × 10-7, OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 × 10-7, OR = 1.47)., Conclusion: We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.

Background: Currently, large populations have been vaccinated against COVID-19. The whole inactivated Sinopharm COVID-19 vaccine has been the main available COVID-19 vaccine in Iran. Ocular inflammatory reactions have been reported following vaccination. The present case reports aim to introduce four cases of uveitis after the Sinopharm vaccine administration. Case presentation: Our first reported case is a 38-year-old woman with a positive medical history of inactive ulcerative colitis. Active uveitis had developed following the second dose of the COVID-19 vaccination. The remaining three cases were healthy individuals who developed the first episode of uveitis, after the COVID-19 vaccine administration. Vogt-Koyanagi-Harada syndrome was the final diagnosis in one of the aforementioned cases. All four patients demonstrated favorable responses to corticosteroid treatment. Conclusion: These observations are in line with incoming reports from all around the world and raise concerns about the possibility of post-vaccination uveitis development, especially in cases with a previous history of auto-immune systemic diseases or inactive uveitis. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a clinicopathologically heterogeneous chronic autoimmune disorder affecting different organs and tissues. It has been reported that there is an increasing rate of SLE incidence among Iranian population. Moreover, the Iranian SLE patients have more severe clinical manifestations compared with other countries. Therefore, it is required to introduce novel methods for the early detection of SLE in this population. Various environmental and genetic factors are involved in SLE progression. Main body: In present review we have summarized all of the reported genes which have been associated with clinicopathological features of SLE among Iranian patients. Conclusions: Apart from the reported cytokines and chemokines, it was interestingly observed that the apoptosis related genes and non-coding RNAs were the most reported genetic abnormalities associated with SLE progression among Iranians. This review clarifies the genetics and molecular biology of SLE progression among Iranian cases. Moreover, this review paves the way of introducing an efficient panel of genetic markers for the early detection and better management of SLE in this population. [ABSTRACT FROM AUTHOR]

Objective: Behcet's disease (BD) is a rare vasculitis that results in multi-organ inflammatory disease. At-risk populations are most prevalent in the Middle East and East Asia. Clinical data on BD in Western countries, especially in the United States, are scarce. We have compared clinical patterning of BD vasculitis in two geographically defined patient cohorts in the Western United States and Iran. Methods: Comparative analysis of a retrospective cohort of 56 patients with BD evaluated at Stanford University Hospital between 2000 and 2016 and a cohort of 163 patients from the BD Registry at Tehran University of Medical Sciences. Clinical, demographic, laboratory, and treatment data were available. Comparisons were performed using descriptive statistics, Student's t-test, and χ2-test. Results: The Stanford patients with BD were significantly younger at disease onset, had a higher proportion of females, and had longer disease duration than Iranian patients with BD. Genital ulcers, skin, joint, neurological, vascular, cardiopulmonary manifestations were all significantly more common in the Stanford cohort and 38% of Stanford patients had four or more organ systems involved compared with approximately 10% of Iranian patients. In contrast, Stanford patients had fewer ocular lesions (Stanford 21.4% vs. Iran 53.4% p<0.05), with the biggest difference seen for retinal vasculitis. Conclusion: Patients with BD from the Western US have a more severe disease course when compared to Iranian patients with BD, as demonstrated by earlier onset and a higher rate of multi-organ involvement. The high risk of Iranian patients with BD developing vasculitis of ocular structures suggests distinct pathomechanisms driving ocular versus extra-ocular BD. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile-onset systemic lupus erythematosus is a multigenic autoimmune disorder. Polymorphisms ofMECP2gene have been reported to increase the risk of adult-onset SLE. In this study, we aimed to analyze ifMECP2gene polymorphisms could impress the proneness to JSLE in Iranian population.Material and Methods: Polymorphisms ofMECP2gene were genotyped in 50 Iranian JSLE patients and 426 matched healthy controls employing the real-time PCR allelic discrimination technique.Results: None of the alleles and genotypes ofMECP2gene SNPs had significantly different distribution between patients and controls. The CTAT haplotype was represented more frequently and significantly in JSLE cases than in controls. A strong linkage disequilibrium was observed among the variants.Conclusions: Although adult-onset SLE had been associated withMECP2gene variants, this gene is not associated with disease susceptibility in JSLE patients, implying the involvement of different susceptibility genes in the pathogenesis of SLE and JSLE. [ABSTRACT FROM PUBLISHER]

Aim: The aim of this case-control study was to investigate association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients. Background: Interleukin 21 (IL-21) has a significant function in the regulation of cellular immune responses. Its exclusive receptor, IL- 21R, expressed on the surface of T, B and NK cells and is important for the proliferation and differentiation of these immune cells. Hence, it was suggested to be involved in response to viral infections. Methods: This study follows a case-control study design and blood samples were collected from 290 patients with chronic HCV and 290 controls for both genes. Genomic DNA was extracted and then for each position, SNP was genotyped by the dedicated PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using logistic regression and Chi-square tests. Results: Genotype frequencies of GG, GT and TT in IL21 gene (rs3093390) were found to be 27.6%, 48.3%, 24.1% and 25.2%, 55,5%, 19,3% respectively in HCV infected patients and control group. For IL21R gene (rs2055979) genotype frequencies of CC, CT and TT were 63.8%, 31.4%, 4.8% and 61.4%, 29.7%, 9.0% respectively in HCV infected patients and control group. P values for genotype and allele frequencies were p=0.188, p=0.769 for IL21 gene, and p=0.144, p=0.179 for IL21R gene respectively. Conclusion: As a result, there is no evidence for an association between IL-21 (rs2055979) and IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients. [ABSTRACT FROM AUTHOR]

Coronavirus infections, known as COVID-19, can induce a fatal respiratory system infection and also affect other organs, such as the kidney and heart. The mortality rate has been estimated between 1 and 5% in previous reports; however, the mortality and morbidity can be higher in patients with the immune-deficiency condition. Rheumatoid arthritis (RA) is one of the most rheumatoid disorders, and it is important to report their clinical and paraclinical data when affected with COVID-19. Evidence about their laboratory and radiologic findings is limited. In this case series, 10 cases of chronic and approved rheumatoid arthritis (RA) affected by COVID-19 are presented. Only 40% had dry cough, but myalgia and weakness as the general first presentation of infections was reported in most cases (80%). Gastrointestinal symptoms, including nausea/vomiting, diarrhea, anorexia, and abdominal pain, were reported in 50% of individuals. In blood cell count, 30% of cases had thrombocytopenia, and ESR in all cases was positive. Abnormal CRP and elevated LDH were seen in 90% of cases. In HRCT assessment, all cases had an abnormal parenchymal pattern, and 90% of cases presented the usual pattern of COVID-19 (bilateral multifocal GGO/consolidation). Although it is a limited report, these findings are helpful for comparison of clinical and paraclinical cases in RA cases with normal cases.

Background: Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD., Methods: In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted., Results: The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups., Conclusions: Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression., (© 2020 John Wiley & Sons, Ltd.)

Despite that the association of Behçet's disease (BD) with the HLA-B5 was first established in the 1970s, a number of recent genome-wide association studies have both confirmed and furthered this association-in various populations-to individual SNPs both inside and outside the HLA. The former include HLA-B, MICA, and HLA-A, while the latter encompass IL10 and IL23R-IL12RB2 regions. The present study examined whether some of these SNPs could be replicated in an Iranian population, where the prevalence of disease is amply documented. Eight SNPs were selected and tested in 552 patients and 417 controls. These were rs7539328, rs12119179, rs1495965, rs1518111, and rs1800871 in IL10 and IL23R-IL12RB2 regions and rs114854070, rs12525170, and rs76546355 (formerly rs116799036) in the HLA locus. The well-known BD-associated genes HLA-B and MICA were independently genotyped. Although we were not able to formally replicate the association with IL10 and IL23R- IL12RB2, we do report that BD in Iran is strongly associated with HLA-B*51, MICA-A6, and the three HLA-linked SNPs (odds ratio (OR) = 3.38, P = 6.21 × 10; OR = 2.08, P = 1.58 × 10; and OR = 1.67-4.05, P = 1.45 × 10 to 4.79 × 10, respectively). Our data further indicate that the robust HLA-B/MICA association may be explained by a single variant (rs76546355) between the two genes. Overall, these data contribute to a better appraisal of the intriguing linkage between BD and the ancient Silk Route, spanning from the Mediterranean shores to Japan. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to compare the interferon-induced protein 44-like (IFI44L) promoter methylation level between systemic lupus erythematosus (SLE) patients and healthy controls and to evaluate its diagnostic value in SLE. Materials and Methods: The IFI44L promoter methylation level was measured in 49 patients with SLE and 50 healthy controls. Quantitative analysis of promoter methylation IFI44L gene in genomic DNA samples extracted from peripheral blood mononuclear cells was examined in SLE patients and healthy controls. The level of DNA methylation was compared between SLE patients and healthy controls as well as within SLE patient groups based on the presence of renal involvement. Moreover, diagnostic values of IFI44L were calculated. Results: The IFI44L promoter methylation level in SLE patients was significantly lower than healthy controls (median, 43.8 vs. 57, respectively; P = 0.008). The level of IFI44L promoter methylation was not significantly different between SLE patients with renal involvement and SLE patients without renal involvement (84.6% vs. 92.7%, respectively; P = 0.774). The IFI44L promoter methylation level ≤94.3% was the best cutoff point with a sensitivity of 91.8% and a specificity of 38% to distinguish patients with SLE from healthy individuals. Conclusion: The level of IFI44L promoter methylation from whole peripheral blood in Iranian SLE patients was significantly lower than healthy controls. Furthermore, the DNA methylation level of IFI44L promoter was not associated with renal damage in patients with SLE. [ABSTRACT FROM AUTHOR]