作者
J. Luo,Q. Y. Su,Y. Zhang,B. Hu,Y. Zhang,Haoyu Zhou,X. Li,Xi Li,C. Wang,S. X. Zhang
摘要
Background Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease which involves in multiple tissue and organ injury. Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating properties. Interestingly, different subsets of Bregs have distinct markers and phenotypes and participate in self immune regulation by different ways. However, the level of Bregs in SLE remains debated. Objectives This study aims to clarify the proportions of Bregs with special controversial cellular markers and Breg-related cytokines in SLE patients. Methods We explored the proportion of Bregs and Breg-related cytokines (IL-10) in SLE patients by searching literature through November 2021 from CBM, CNKI, China Science and Technology Journal Database, Wan Fang Data, PubMed, Embase, Web of Science, Cochrane Library and Medline. Random effects model was used to pool data. Heterogeneity and risk of bias was examined with I-squared index (I 2 ) statistic. Inconsistency was evaluated by using the I 2 and Egger tests were used for the evaluation of potential publication bias (STATA v.12.0). Results Total 14 case-control studies involving 489 PsA patients and 330 healthy controls (HCs) were included in this study (Table 1). No significant difference in the proportions of Bregs was evident between SLE patients and HCs[SMD=0.067, 95%CI (-0.924,1.059), P=0.894]. Because of a significant statistical heterogeneity observed [I 2 =97.1%, p<0.001], we conducted sub-analyses based on individual definitions of Bregs. We found the proportions of CD19 + CD24 hi CD38 hi Breg cells was significantly increased in SLE [SMD=0.902, 95%CI (0.157,1.647), P<0.001](Figure 1A). The level of serum IL-10 was increased in SLE compared to that of HCs [SMD=1.062, 95%CI (0.754,1.370), P<0.001] with no publication bias based on the Egger tests (t=0.91, P=0.366)(Figure 1B). Table 1. Characteristics of the individual studies included in the meta-analysis. Author Publish Year EI a Q b Case Numbers Breg’s definition Mean % of Breg (mean(or median)±SD) % of Breg among PBMC/CD19 + T cells SLE HC Blair,P.A 2010 4 6 25 14 CD19 + CD24 hi CD38 hi SLE: 13.9±5.21 PBMC HC: 9.02±2.71 Wang,T. 2017 4 7 56 35 CD19 + CD24 hi CD38 hi SLE: 39.83±21.39 PBMC HC: 8.74±3.97 Wang,H. 2019 4 6 36 30 CD19 + CD24 hi CD38 hi SLE: 12.94±5.45 PBMC HC: 5.64±3.13 Simon,Q 2016 4 6 16 33 CD19 + CD24 hi CD38 hi SLE: 17.9±7.2 PBMC HC: 11.65±4.01 Zhuo-long Wang 2018 4 6 28 30 CD19 + CD24 hi CD38 hi SLE: 3.62±1.25 PBMC HC: 4.07±1.48 Heinemann,K. 2016 4 6 33 21 CD19 + CD24 hi CD38 hi SLE: 1.6±2.6 PBMC HC: 1.5±1.1 Chu,M. 2015 4 7 43 32 CD19 + CD24 high CD27 + SLE: 8.39±7.22 PBMC HC: 26.58±8.96 Vadasz,Z. 2015 4 6 21 20 CD19 + CD25 hi FoxP3 hi SLE: 18.5±3.05 PBMC HC: 11±1.65 Cai,X. 2015 4 7 60 20 CD19 + CD5 + SLE: 1.86±0.8 PBMC HC: 4.35±1 Yang,X. 2014 4 7 30 15 CD19 + CD5 + CD1d hi SLE: 4±1.57 PBMC HC: 1.63±0.99 Shan-feng Liu 2015 4 6 10 10 CD19 + CD5 + CD1d hi SLE: 0.83±0.28 CD19 + B cell HC: 0.2±0.21 Zhong-wei Huang 2014 4 5 34 30 CD19 + CD5 + CD1d hi SLE: 7.86±4.1 PBMC HC: 22.71±9.17 Ye, Z. 2019 4 6 47 20 CD19 + IL-10 + SLE: 0.1±2.78 CD19 + B cell HC: 4.85±4.54 Rong-wei Zhang 2016 4 6 50 20 CD19 + IL-35 + SLE: 1.77±0.79 PBMC HC: 4.24±1.11 SLE: systemic lupus erythematosus. a Evidence level (EL) of each study was based on Oxford Center for Evidence-Based Medicine 2011. b Quality (Q) of each study was based on the Newcastle-Ottawa Quality Assessment Scale case. Figure 1. Conclusion The levels of CD19 + CD24 hi CD38 hi Bregs and IL-10 were significantly increased in SLE patients, suggesting that the abnormalities of Bregs numbers and function are the critical causes in the development of SLE. Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 82001740). Disclosure of Interests None declared