Regulatory T cells in patients with early untreated rheumatoid arthritis: Phenotypic changes in the course of methotrexate treatment
Regulatory T cells in patients with early untreated rheumatoid arthritis: Phenotypic changes in the course of methotrexate treatment
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DOI：
10.1016/j.biochi.2020.03.014
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发表时间：
2020-07-01
期刊：
影响因子：
3.9
通讯作者：
Nasonov, Eugene
中科院分区：
文献类型：
--
作者：
Avdeeva, Anastasia;Rubtsov, Yury;Nasonov, Eugene
类风湿性关节炎（Rheumatoid arthritis，RA）是一种常见的全身性自身免疫性疾病，其特征是胶原特异性T辅助细胞过度活化，血清中自身抗体水平升高。RA的发生与调节性CD4+Foxp3+T细胞（Treg）的区室缺陷相关，但关于RA患者中Treg群体的抑制潜力的数据是矛盾的，并且取决于疾病的阶段。在这项研究中，我们的目的是表征CD4+Foxp3+Treg的丰度和表型标志物在健康供体的外周血相比，未经治疗的早期RA患者，以找到潜在的相关性与疾病的活动，抗体水平，和绝对数量和不同的T细胞亚群的比例。此外，我们评估了甲氨蝶呤（MT）治疗对未经治疗的早期RA患者外周血中CD4+Foxp3+Treg的百分比和绝对数量的影响。我们证明了Treg群体的增加和表型变化与对MT的应答密切相关。对匹配的RA患者（n = 45）和健康对照（n = 20）的群组的分析显示，与健康对照相比，患有未治疗的早期RA的患者显示出血液Treg百分比和绝对数量的显著降低，以及活化的Treg表面标志物的低水平。Treg区室的缺陷与RA活性和抗体水平均呈负相关。MT治疗早期未经治疗的RA患者增加了具有高水平活化标志物的Treg的比例和绝对数量，表明其功能能力增加。在这里，我们推测的作用，作为特定的细胞标志物成功的RA治疗。(C)2020作者（S）由爱思唯尔公司出版
Rheumatoid arthritis (RA) is frequent systemic autoimmune disease characterized by excessive activation of collagen-specific T helper cells, and elevated level of autoantibodies in the serum. Development of RA is associated with defect in compartment of regulatory CD4+Foxp3+T cells (Treg), but data concerning suppressive potential of Treg population in RA patients are contradictory and depend on the stage of disease. In this study we aimed to characterize abundance and phenotypic markers of CD4+Foxp3+Treg in peripheral blood of healthy donors compared to untreated early RA patients to find potential correlations with the disease activity, antibody level, and absolute numbers and proportion of different subpopulations of T cells. Moreover, we assessed the influence of methotrexate (MT) treatment on percentage and absolute numbers of CD4+Foxp3+Treg from the peripheral blood of untreated early RA patients. We demonstrate that increase and phenotypic changes in Treg population correlate well with response to MT. Analysis of the cohorts of matched RA patients (n = 45) and healthy controls (n = 20) revealed that patients with untreated early RA demonstrate substantial decrease in blood Treg percentage and absolute number, as well as low level of activated Treg surface markers in comparison to healthy control. The defect in Treg compartment negatively correlates with both RA activity and antibody level. MT treatment of patients with early untreated RA increases both proportion and absolute number of Treg with high level of activation markers, suggesting an increase of their functional capacity. Here we speculate the role of Tregs as specific cellular marker of successful RA treatment. (C) 2020 The Author(s). Published by Elsevier B.V.