Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy; Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
EBioMedicine. 2015 Nov 17;2(12):2037-45. doi: 10.1016/j.ebiom.2015.11.019. eCollection 2015 Dec.
Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB104. The Collagen IIp261-273-specific T cell repertoire in the peripheral blood of DR4 + patients at the onset of the disease shows a restricted TCR-beta chain usage among which the most frequent is TRBV25. To define whether this group of DR4-restricted collagen-specific shared T cell could represent markers of active-severe disease and response to therapy, 90 subjects affected by early-RA were enrolled in the study; peripheral blood mononuclear cells were cultured with or without the human collagen II peptide p261-273 and were examined by immunoscope analysis for the usage of the previously identified shared TCR-beta chains. We report that the presence of T cells carrying rearrangement TRBV25 associated with HLA-DR haplotype and disease activity. HLA-DRB1 haplotypes 04-04, 04-01 and 04-11 were significantly associated with usage of TRBV25, higher disease activity at the onset of disease and poor response to DMARDs. Finally, the HLA-DRB1* haplotype appeared complementary with current serologic tools to predict good and poor responders in a treat to target strategy. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients.
类风湿关节炎（RA）的特征是慢性关节炎症，并与 HLA-DRB104 相关。疾病发作时，DR4+患者外周血中的 II 型胶原 p261-273 特异性 T 细胞库显示出受限的 TCR-β链使用，其中最常见的是 TRBV25。为了确定这群 DR4 限制性胶原特异性共享 T 细胞是否可以作为活动期严重疾病和治疗反应的标志物，研究纳入了 90 例早期 RA 患者；外周血单核细胞在存在或不存在人类 II 型胶原肽 p261-273 的情况下培养，并通过免疫谱分析检查先前确定的共享 TCR-β链的使用情况。我们报告携带与 HLA-DR 单倍型和疾病活动相关的重排 TRBV25 的 T 细胞的存在。HLA-DRB1 单倍型 04-04、04-01 和 04-11 与 TRBV25 的使用显著相关，疾病发作时疾病活动度更高，对 DMARDs 的反应较差。最后，HLA-DRB1* 单倍型似乎与当前的血清学工具互补，以在靶向治疗策略中预测良好和不良反应者。这里报告的数据为预测疾病过程和预见 RA 患者的个体化治疗提供了线索。
