Department of Vascular Problems in Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, 115522, Moscow, Kashirskoe Shosse 34A, Russian Federation.
Department of Medicine, Lomonosov Moscow State University, 119991, Moscow Lomonosovsky Prospect, 27/1, Russian Federation; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997, Moscow, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Russian Federation.
Biochimie. 2020 Jul;174:9-17. doi: 10.1016/j.biochi.2020.03.014. Epub 2020 Apr 7.
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.
类风湿关节炎（RA）是一种常见的系统性自身免疫性疾病，其特征为胶原特异性辅助性 T 细胞过度激活，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）区室缺陷有关，但关于 RA 患者 Treg 群体的抑制潜力的数据存在矛盾，并且取决于疾病的阶段。在这项研究中，我们旨在比较健康供体与未经治疗的早期 RA 患者外周血中 CD4+Foxp3+Treg 的丰度和表型标志物，以寻找与疾病活动、抗体水平以及不同 T 细胞亚群的绝对数量和比例相关的潜在相关性。此外，我们评估了甲氨蝶呤（MTX）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 Treg 群体的增加和表型变化与 MT 反应密切相关。对匹配的 RA 患者队列（n=45）和健康对照组（n=20）的分析表明，与健康对照组相比，未经治疗的早期 RA 患者血液 Treg 百分比和绝对数量明显减少，并且 Treg 表面激活标志物水平较低。Treg 区室缺陷与 RA 活性和抗体水平呈负相关。未经治疗的早期 RA 患者的 MT 治疗增加了 Treg 的比例和绝对数量，同时伴有高水平的激活标志物，提示其功能能力增强。在这里，我们推测 Treg 作为成功 RA 治疗的特定细胞标志物的作用。
