To systematically review and assess the efficacy and safety of hydroxychloroquine (HCQ) for treating primary Sjogren’s syndrome (pSS). Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane Library) were searched for randomized controlled trials and retrospective or prospective studies published in English that reported the effect of HCQ on pSS. The subjective symptoms (sicca symptoms, fatigue and pain) and the objective indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main outcome measures. A meta-analysis and descriptive study on the efficacy and safety of HCQ were conducted. The estimate of the effect of HCQ treatment was expressed as a proportion together with 95% confidence interval, and plotted on a forest plot. Four trials with totals of 215 SS patients, including two randomized controlled trials, one double blind crossover trial and one retrospective open-label study, were analyzed in this review. For dry mouth and dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The efficacy of HCQ in treating pain associated with pSS was superior to that of the placebo. There was no significant difference between HCQ-treated groups and controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte sedimentation rate compare with placebo. A descriptive safety assessment showed that gastrointestinal adverse effects were the most common adverse effects associated with HCQ. This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS. Well-designed, randomized, controlled trials are needed to provide higher-quality evidence to confirm our findings, and future studies should focus on some other index or extraglandular measures, such as cutaneous manifestations, to further explore the therapeutic effect of HCQ in pSS.

Sjögren’s syndrome (SS) is an autoimmune disease primarily affecting salivary glands, with xerostomia as a distinct clinical manifestation. This disease also poses a significantly increased risk of lymphoma, severely impacting patients’ quality of life. The imbalance between Th17 and Treg cells plays a critical role in SS progression, driving severe immune dysregulation, chronic inflammation, and escalating tissue dysfunction. However, current clinical treatments for SS still remain limited, and it continues to be recognized as a refractory disease. Therefore, the development of novel and effective therapeutic strategies is a pressing demand in clinical research. In recent years, extracellular vesicle (EV) therapy has emerged as a promising approach for autoimmune disease treatment, showing encouraging outcomes in modulating immune balance and alleviating symptoms. EVs carry diverse cargo, among which microRNAs (miRNAs) are highly abundant and play critical roles. These small RNAs are essential for EV-mediated functions, particularly in regulating gene expression and modulating the immune microenvironment. Our research team first isolated labial gland mesenchymal stem cells (LGMSCs) and their derived EVs (LGMSC-EVs), which offer potential therapeutic advantages in SS due to their salivary gland origin. Then we screened and identified the highly enriched miRNA let-7f-5p as a key regulator through miRNA profiling analysis. To achieve better therapeutic outcomes, we transfected exogenous miRNA let-7f-5p into LGMSC-EVs to upregulate its expression, thereby constructing let-7f-5p-encapsulated LGMSC-EVs. These modified EVs were subsequently tested in an experimental SS mouse model to evaluate their therapeutic potential. The upregulation of miRNA let-7f-5p in LGMSC-EVs significantly enhanced their therapeutic effects, resulting in clinical improvements such as increased salivary flow and reduced lymphocytic infiltration. Mechanistically, let-7f-5p-encapsulated LGMSC-EVs suppressed Th17 cells by directly targeting the 3’-untranslated region (3’UTR) of RORC, inhibiting the RORC/IL-17A signaling axis, and reducing IL-17A production, thereby restoring Th17/Treg balance and promoting an anti-inflammatory profile. Collectively, this let-7f-5p-encapsulated LGMSC-EV therapy offers a promising target-driven approach for the treatment of SS, achieving improved clinical outcomes and immune rebalance after modification with miRNA let-7f-5p, which presents new potential for the clinical treatment of SS.

Background: Pemphigus vulgaris (PV) is a potentially fatal autoimmune bullous disease. The role of microRNA (miRNA, miR) in the diagnosis and pathogenesis of PV remains unknown. This study aims to provide potential miRNA biomarkers for PV diagnosis and therapy options. Methods: Serum samples were obtained from 22 PV patients, 15 mucous membrane pemphigoid (MMP) patients, and 10 normal controls (NC). Total RNA was extracted from the serum samples, and 12 selected miRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses including target gene prediction and enrichment analysis were performed. Results: Twelve miRNAs were increased in the serum of the PV group compared with the NC group, in which six miRNAs had good efficacy to diagnose PV from MMP with the area under the receiver operator characteristic curves of 0.970 to 0.988. A series test for the combination of miR-584-5p and miR-155-5p reached the sensitivity and specificity of 95.5% and 100%. Bioinformatic analysis revealed target gene enrichment in the cell adhesion pathways, immune-relating pathways, and P38 mitogen-activated protein kinases signaling pathway. Conclusion: The study provides new insights and targets of miRNAs for the precise diagnosis and the exploration of pathogenesis for PV, which may serve as a reference for further research into autoimmune bullous diseases.

Primary Sjögren's syndrome is a prototypical autoimmune disease, with B cell dysfunction as a dominant feature. Further insights into distribution of B cell subsets in primary Sjögren's syndrome are urgently required to identify the most appropriate target subpopulation. We aimed to evaluate the profiles of B lymphocyte subpopulations in primary Sjögren's syndrome patients and to investigate their clinical significance. Thirty primary Sjögren's syndrome patients and 15 age-and sex-matched healthy controls were recruited. Peripheral B cell subsets were analyzed by flow cytometry. Compared to healthy controls, circulating CD19⁺ B cells, CD19⁺CD20⁻ B cells, CD19⁺CD27⁻IgD⁺ naïve B cells, CD19⁺IgD⁺CD38^high plasmablasts, CD19⁺CD24^highCD38^high transitional B cells and CD19⁺CD20⁻CD27⁺CD38⁺ plasma cells were elevated in patients with primary Sjögren's syndrome, whereas CD19⁺CD27⁺ memory B cells, CD19⁺CD27⁻IgD^- double negative B cells and CD19⁺CD24^hiCD27⁺ Bregs were decreased. Furthermore, the percentage of circulating CD19⁺CD20⁻CD27⁺CD38⁺ plasma cells was positively correlated with serum IgG levels and the proportional area of lymphocytic infiltration of labial gland. We identified a comprehensive B lymphocyte subset distribution profile in primary Sjögren's syndrome. Moreover, we detected a clinical significance of CD19⁺CD20⁻CD27⁺CD38⁺ plasma cells, suggesting that these cells might play a key role in disease pathology and represent potential therapeutic targets.