Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan.
Dis Markers. 2019 Jul 7;2019:2364943. doi: 10.1155/2019/2364943. eCollection 2019.
Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.
类风湿关节炎（RA）是一种系统性自身免疫性疾病，主要导致患者慢性多关节炎症和关节损伤。为治疗 RA，已使用生物疾病修饰抗风湿药物（bDMARDs）通过靶向和调节免疫系统来减少炎症并干扰疾病进展。尽管 bDMARDs 在 RA 患者中的治疗效果已被广泛报道，但这些药物是否在 T 细胞库状态中也发挥重要作用仍不清楚。因此，我们设计了这项研究，以确定不同类型 bDMARD 治疗的 RA 患者的 T 细胞库特征的作用。我们应用高通量测序方法对接受阿达木单抗（抗 TNF-）治疗的 8 例患者的循环 T 淋巴细胞的 T 细胞受体β链（TCRβ）库进行了分析，这些患者中有/没有联合使用利妥昔单抗（抗 CD20）或托珠单抗（抗 IL6R）。随后，我们分析了 TCRβ库的克隆多样性和 CDR3 长度分布的差异，以及 TCRβ库的 V 和 J 基因的使用，并探讨了 RA 患者接受 bDMARD 治疗后，多样性与疾病活动之间的关联。所有患者在不同药物治疗方案后 DAS28 评分（<2.6）均得到良好控制，TCRβ库的多样性、CDR3 长度分布和 V 和 J 基因的使用无显著统计学差异。然而，所有接受 bDMARD 治疗的 RA 患者的整体 TCRβ库多样性与疾病活动评分之间存在趋势。此外，发现年龄与接受 bDMARD 治疗的 RA 患者的库多样性相关。通过对接受不同生物药物治疗的 RA 患者的 TCR 库进行分析，我们的研究表明，RA 患者在接受生物治疗后，TCR 库多样性与疾病活动之间呈负相关。
