类风湿关节炎患者外周血记忆B细胞池分布特征及治疗对其的影响

Disturbance of peripheral blood B cells homeostasis in rheumatoid arthritis and the influence of therapy on B cells homeostasis

目的 探索B细胞亚群在RA患者外周血的分布特征、与RA临床指标的相关性及治疗对其的影响,从而进一步了解B细胞在RA的发病机制中的作用.方法 用流式细胞仪检测141例RA患者和33名健康对照外周血细胞表面标记CD19、CD27、免疫球蛋白（Ig）D,观察转换后记忆B细胞（CD19＋CD27＋IgD-）、转换前记忆B细胞（CD19＋CD27＋IgD＋）、幼稚B细胞（CD19＋CD27-IgD＋）、双阴B细胞（CD19＋CD27-IgD-）的分布,RA患者根据治疗分为TNF-α拮抗剂治疗组、传统DMARDs治疗组及初发未治疗组.了解其与临床表现、实验室检查间的关系及不同治疗对B细胞亚群分布的影响.采用SPSS 23.0分析软件,采用独立样本t检验,单因素方差分析,相关性分析用Spearman相关分析.结果 ①RA初发未治疗患者（病程〈3个月）外周血中转换前记忆B细胞的比率[（8±4）％]明显低于健康对照[（13±4）％]（t=3.3,P〈0.05）,转换后记忆B细胞比率[（18±10）％]低于健康对照[（23±7）％]（t=2.2,P〈0.05）;②RA患者转换前记忆B细胞（CD19＋CD27＋IgD＋）的比率和RA疾病活动度评分DAS28呈负相关（r=-0.23,P〈0.05）;③RA患者转换前记忆B细胞（CD19＋CD27＋IgD＋）的比率和ESR、IgG呈负相关,但与CRP、RF、抗环瓜氨酸肽抗体（ACPA）之间无明显相关性;④经过TNF-α拮抗剂治疗或传统DMARDs治疗转换后记忆B细胞及转换前记忆B细胞比率有所回升,但差异无统计学意义.结论 RA初发患者外周血中存在B细胞亚群分布异常,主要表现为转换后记忆B细胞及转换前记忆B细胞的比率降低;同时转换前记忆B细胞的比率和DAS28评分及ESR、IgG水平呈负相关;TN F-α拮抗剂及传统治疗均对RA患者外周血部分B细胞亚群的分布有一定影响,说明B细胞亚群分布改变可能在RA疾病发生发展中起重要作用.

Objective To investigate the characteristics and the frequencies of B cell subsets in peripheral blood of rheumatoid arthritis （RA） patients,and to study the correlation between B cell subsets and clinical indices and influence of different therapies on B cell subsets to deeply understand the pathogenesis of RA.Methods Peripheral blood witched memory B cells,non-switched memory B cells,naive B cells,and double negative B cells of 141 patients and 33 healthy controls were measured by flow cytometry.Patients were divided into three groups based on their therapeutic regimen,including tumor necrosis factor-or （TNF-α） inhibitors combined with disease modifying antirheumatic drugs （DMARDs）,DMARDs only and patients without any therapy.The relevance between B cells subsets and clinical manifestations,lab test results exemption were assessed as well as the influence of different therapies.All data were were analyzed by Statistical product and service solutions （SPSS） 23.0 statistical analysis for unpaired t test,analysis of variance and Spearman＇s correlations analysis.Results ① New-onset RA patients with less than 12 weeks disease duration and never accepted any drugs had a significantly lower frequency of peripheral blood memory B cells,including non-switched memory B cells [（8 ±4）% vs （13 ±4）%,P〈0.05,t =3.3）] and switched memory B cells [（18±10）% vs （23±7）%,P〈0.05,t=2.2）],than healthy individuals.② There was a negative association between non-switched memory B cells and disease activity score in 28 joints （r=-0.23,P〈0.05）.③ Negative association between non-switched memory B cells and erythrocyte sedimentation rate （ESR）,lgG was found,while therewas no association between pre-switched B cells and other laboratory test results.④ Non-switched memory B cells and switched memory B cells increased after TNF-α arntagonist or DMARDs therapy.Conclusion The results of this study suggest that B cell abnormalities in new-onset RA patients with short disease duration are reduced non-switched memory B cells and switched memory B cells.A negative correlation has been found between non-switched memory B cells and ESR and lgG.B cells subsets frequency are changed by TNF-α antagonist and DMARDs,which suggests that changes of B cell subsets may contribute to the occurrence and development of RA.