Regulatory B cells in ANCA-associated vasculitis
Regulatory B cells in ANCA-associated vasculitis
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DOI：
10.1136/annrheumdis-2012-202986
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发表时间：
2013-08-01
影响因子：
27.4
通讯作者：
Tervaert, J. W. Cohen
中科院分区：
文献类型：
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作者：
Wilde, B.;Thewissen, M.;Tervaert, J. W. Cohen
目的B细胞具有作为抗原提呈细胞的免疫调节功能。产生IL-10的B细胞(BREG)的一个单独的亚群调节T细胞介导的免疫已被发现。本研究探讨BREG在抗中性粒细胞胞浆抗体相关性小血管炎(AAV)中的作用。AAV缓解期30例。此外，对11例AAV合并活动期疾病的患者进行了研究。BREG定义为IL-10(+)CD19(+)B细胞，经胞嘧啶-磷酸-鸟苷脱氧核苷酸(CpG ODN)2006培养。用流式细胞术检测CD4(+)、CD127(低)、CD25(Hi)、CD39(Neg)/CD39(+)调节性T细胞(Treg)、干扰素(IFN)(+)、IL-4(+)和IL-17A(+)T辅助细胞亚群。干扰素+T辅助细胞的频率与缓解期AAV患者的BREG呈负相关，而在活动性小血管炎或HCS患者中则不相关。有趣的是，AAV静止期患者的Treg细胞总数和CD39(+)Treg亚群与BREG呈正相关。结论AAV患者产生IL-10的B细胞减少。此外，Breg可能调节Th1细胞，并与静止期AAV中的Treg相关。在活动期AAV中，BREG对Th1细胞的抑制可能是不够的。
Objectives B cells have immunoregulatory function acting as antigen-presenting cells. A separate subset of interleukin (IL)-10 producing B cells (Breg) regulating T cell mediated immunity has been identified. In the present study, we investigated the role of Breg in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV).Methods 17 healthy controls (HCs) and 41 patients with AAV were enrolled. 30 patients with AAV were in remission. Furthermore, 11 patients with AAV with active disease were studied. Breg were defined as IL-10(+)CD19(+) B cells upon culture with cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) 2006. Next to Breg, CD4(+)CD127(low)CD25(hi)CD39(neg)/CD39(+) regulatory T-cells (Treg), interferon (IFN)(+), IL-4(+) and Il-17A(+)T helper cell subsets were determined via flow cytometry.Results Patients with active or quiescent disease showed a diminished fraction of Breg as compared with HCs. The frequency of IFN+ T helper cells was negatively associated with Breg in untreated AAV in remission but not in active vasculitis or in HCs. Interestingly, the total Treg population and the CD39(+) Treg subpopulation correlated positively with Breg in inactive patients with AAV.Conclusions IL-10 producing B cells are diminished in AAV. Furthermore, Breg might regulate Th1 cells and are associated with Treg in quiescent AAV. Suppression of Th1 cells by Breg may be insufficient in active AAV.