Background: Rituximab has been widely proposed to treat systemic sclerosis (SSc) by depletion of pathogenic B cells. Nonetheless, the clinical benefit of Rituximab in SSc remains contentious.Objective: This meta-analysis was conducted to systematically evaluate the safety and efficacy profile of Rituximab in SSc patients.Methods: We performed a systematic online query in PubMed, Cochrane, and Web of science.Available studies about the assessment of Rituximab in SSc patients were comprehensively reviewed and investigated.Results: In total, 14 studies comprising 597 participants were enrolled in our analysis. Pooled results showed the durable improvement of mRSS for skin involvement (∆mRSS: 7.00 at 6-month, 9.70 at 12month, and 10.93 at 24-month), while FVC (∆FVC: -0.69 at 6-month, -2.62 at 12-month, -0.67 at 24month) and DLCO (∆DLCO -2.39 at 6-month, -3.28 at 12-month, -0.79 at 24-month) for lung involvement remain stable in SSc patients after Rituximab treatment. And safety profile of Rituximabrelated adverse events rate was 12% in the pooled result. Conclusion:The pooled results of this meta-analysis indicated that Rituximab was well-tolerated, and it was able to generate improvement of cutaneous function and stabilization of pulmonary function in SSc patients.

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Background Retinoic acid (RA) is an active metabolite of vitamin A and has been reported to improve the clinical symptoms of patients with systemic sclerosis (SSc). However, the mechanism of RA in the prevention of SSc remains unclear. Regulatory T cells (Tregs) are a subpopulation of T cells with immunosuppressive activity. The quantitative and functional defects of Tregs may mediate the immune dysfunction in SSc. The addition of all-trans retinoic acid (ATRA) to human naïve CD4+ cells could promote the maturation of Tregs and increase the stable expression of Foxp3. In this study, we explored the role of RA on Tregs in SSc CD4+ T cells and its possible epigenetic mechanisms, so as to further understand the mechanisms of RA on SSc. Methods CD4+ T cells were isolated from peripheral blood of SSc and treated with or without ATRA and/or transforming growth factor-β (TGF-β). The percentage of CD4+CD25+FOXP3+ Tregs was counted by flow cytometry. FOXP3 mRNA and protein levels were measured by quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. Bisulfite sequencing was performed to determine the methylation status of the FOXP3 proximal promoter sequences. Results The expression of Tregs and FOXP3 in CD4+ T cells from patients with SSc increased in response to ATRA. Moreover, combined stimulation with ATRA and TGF-β resulted in the enhancement of these effects. Further studies revealed that stimulation with ATRA increased the expression of FOXP3 in SSc CD4+ T cells by downregulating FOXP3 promoter methylation levels. Conclusions ATRA acts as an inducer of Treg response in SSc CD4+ T cells via demethylation of the FOXP3 promoter and activation of FOXP3 expression. This may be one of the molecular mechanisms for ATRA, and therefore, RA can be used for the treatment of SSc.