The Regulatory B Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-analysis

Abstract
Background: The study of regulatory B cells (Bregs) in systemic lupus erythematosus (SLE) has been in full swing in recent years, but the number and function of Bregs in SLE patients have also present quite contradictory results. Therefore, we conducted a meta-analysis to verify the changes in Bregs in active SLE. Methods: We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed, Embase, Web of Science, Cochrane and CNKI. Due to the degree of heterogeneity is very high, we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls. Then, sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity. Results: Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis. The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls [0.259, (−1.150, 1.668), p = 0.719], with great heterogeneity ( I2 = 97.5%) . The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity, but after excluding the article conducted by Cai X and his colleagues, the percentages of Bregs were significantly higher in active SLE than those in controls [1.394, (0.114,2.675), p = 0.033]. The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score ≥ 5, the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739), p = 0.002], but when the threshold of SLEDAI score ≥ 6 chosen for active SLE, the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759), p < 0.001]. Meanwhile, other subgroup analysis based on the different phenotypes of Bregs, diagnostic criteria, enrolled research countries, treatment status, and organ involvement did not differ in proportion of Bregs between SLE patients and controls. Conclusions: The study implies that Bregs may play a role in the pathogenesis of active SLE, and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.