Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission
Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission
复制标题
DOI：
10.1002/art.40430
复制
发表时间：
2018-05-01
影响因子：
13.3
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Chen;Wang, Dongwei;Wang, Hui
Objective.目的检测类风湿关节炎（RA）活动期和稳定缓解期患者外周血中CD 4 + CXCR 5 + FoxP 3+滤泡性Treg（Tfr）细胞的表达和功能变化，探讨Tfr细胞在RA发病机制中的作用。采用流式细胞术检测39例活动期RA患者、39例稳定缓解期RA患者和33例健康对照者外周血中Tfr细胞和滤泡辅助性T（Tfh）细胞水平。通过将Tfr细胞与Tfh细胞和B细胞共培养来测量Tfr细胞的功能。还分析了活化的CD 45 RA-FoxP 3（高）Tfr细胞。检测血清IG、自身抗体等临床指标，并系统分析其与Tfr细胞的相关性。计算28个关节的疾病活动性评分（DAS 28），并与Tfr细胞进行相关性分析。RA稳定缓解期患者外周血CD 4 + CXCR 5 + FoxP 3 + Tfr细胞水平和Tfr细胞/Tfh细胞比值显著高于活动期RA患者和健康对照组。与健康对照组相比，RA稳定缓解期患者Tfr细胞功能增强，活化的CD 45 RA-FoxP 3（high）Tfr细胞亚群增多。RA患者Tfr细胞数与IgG、类风湿因子、抗环瓜氨酸肽及DAS 28呈负相关。随着RA患者达到疾病的稳定缓解，循环Tfr细胞增加，并且增加的Tfr细胞可以抑制RA患者的自身免疫以稳定其病情。我们的研究结果为RA的发病机制提供了新的见解。
Objective. To examine the expression and changes in function of circulating CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis (RA) and in patients with RA in stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA.Methods. Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA, 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD45RA-FoxP3(high) Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with Tfr cells was conducted.Results. The level of CD4+CXCR5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD45RA-FoxP3(high) Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti-cyclic citrullinated peptide as well as with the DAS28.Conclusion. Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.