In our patients the prevalence of cutaneous involvement was similar to those of nearby countries (with similar climate). Renal involvement was seen more than some other countries especially more than European countries, while other manifestations (such as hematologic and joint involvement) were similar to European countries (with similar ethnicity). We may conclude that genetic and/or climatic factors may lead to different presentations of lupus.

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The most prominent feature of systemic sclerosis (SSc) and other diseases associated with fibrosis is the prolonged activation of fibroblasts not eliminated by apoptosis, hence characterized by accumulation of more extra cellular matrix (ECM). We tend to verify if microRNA-29a (miR-29a) as an anti-fibrotic factor could induce apoptosis in SSc fibroblasts. We did not detect apoptosis in SSc fibroblasts. We found that Bcl-2 expression was upregulated in SSc fibroblasts and the ratio of Bax:Bcl-2 in these cells was significantly lower (p = 0.02) compared to normal fibroblasts. Transfection of both SSc and transforming growth factor-β (TGF-β) stimulated fibroblasts by miR-29a mimic, significantly decreased the expression of two anti-apoptotic members of the Bcl-2 family, Bcl-2 (p = 0.0005, p = 0.01) and Bcl-XL (p = 0.0001, p = 0.006), resulted in enhanced Bax:Bcl-2 ratio and induced a high rate of apoptosis. Recently, miR-29 has been introduced as an anti-fibrotic factor with potential therapeutic effect on SSc. Until now, it has not been proposed whether there is a relationship between miR-29a and apoptosis in SSc. According to our results, it seems that miR-29a is a potent inducer of apoptosis in SSc fibroblasts and an attenuator of ECM production in these cells. MiR-29a disrupted the expression profiling of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-XL) which is the central point of dynamic life-death rheostat in many apoptotic pathways. Furthermore, dermal fibroblasts from patients with SSc showed elevation in TNF-α mRNA levels, while restoration of miR-29a decreases TNF-α production in these cells. Although further molecular studies are necessary to investigate the underlying apoptotic pathways, the present findings suggest that anti-fibrotic and pro-apoptotic properties of miR-29a could provide novel benefits toward the development of fibroblast-specific anti-fibrotic therapies.

BackgroundThis study aimed to compare efficacy and safety of test-adalimumab (CinnoRA®, CinnaGen, Iran) to the innovator product (Humira®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA).MethodsIn this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA® or Humira® every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety.ResultsPatients who were randomized to CinnoRA® or Humira® arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA® group was non-inferior to the Humira® group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA® and Humira® groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant.ConclusionCinnoRA® was shown to be non-inferior to Humira® in terms of efficacy at week 24 with a comparable safety profile to the reference product.Trial registrationIRCT.ir, IRCT2015030321315N1. Registered on 5 April 2015.

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In oral corticosteroid subset, younger age of disease onset and psychosis were significantly associated with AVN, whereas malar rash and oral ulcer showed negative association AVN.

Aim: To investigate the impact of gender on expression of systemic lupus erythematosus (SLE) in a cohort of 2355 SLE patients as one of the largest series of cases among the present reports.Method: In this retrospective study we used medical records of all patients (239 male and 2116 female) of the SLE registry of Rheumatology Research Center (RRC), Tehran University of Medical science (TUMS), Iran. Both clinical and paraclinical manifestations of SLE patients have been registered in this database since 1976 and updated during their follow-up. Chi-square test was used to compare the clinical and paraclinical manifestations in men and women at disease onset and during the disease course. We used logistic regression to compute odds ratios with 95% confidence intervals. A P-value < 0.05 was considered as statistically significant.Results: Mean age at disease onset was 25 AE 11.8 and 24.5 AE 10.3 years in men and women, respectively (P = 0.48). Comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of mucocutaneous (43.5% vs. 33.7%, P = 0.005) and a lower prevalence of musculoskeletal symptoms (44% vs. 54.7%, P = 0.003) as the initial manifestation. During the disease course, discoid rash (25.9% vs. 13%, P = 0.000) and type IV lupus nephritis (23.4% vs. 18.1%, P = 0.03) were significantly more common, whereas arthritis (61.1% vs. 71.7%, P = 0.01) and leukopenia (28.5% vs. 35.8%, P = 0.024) were significantly less common in men.Conclusion: This study reveals gender influence on some manifestations of SLE. Considering sex differences is recommended in diagnostic and therapeutic features of the disease.

Background: Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients. Methods: An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein-protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters. Results: A total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues. Conclusions: Analysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.