Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

Abstract

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-α) 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.

Longitudinal analysis of T-cell receptor repertoires reveals persistence of antigen-driven CD4+ and CD8+ T-cell clusters in Systemic Sclerosis

“…for SSc [57][58][59][60]. [20,44,61], and have been proposed as a characteristic of autoimmune repertoires. Interestingly, in SSc, differences in the diversity of the TCR repertoire have also been observed between responders and non-responders after autologous hematopoietic stem-cell transplantation (AHSCT, the only therapy with long-term clinical benefit in SSc), with non-responders having a less diverse repertoire [62].…”

“…High throughput sequencing of TCR repertoires is emerging as a valuable tool to unravel the exact role of T-cells in autoimmune diseases. The TCR repertoire has been proposed to serve as diagnostic biomarker for various autoimmune diseases, and recent studies have identified disease-associated TCR sequences in autoimmune diseases including autoimmune encephalomyelitis (AE), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) [19][20][21]. Moreover, changes in T-cell repertoire diversity have been suggested to predispose the pathological manifestations in RA patients [22].…”

VAV1 Gene Polymorphisms in Patients with Rheumatoid Arthritis

“…Rheumatoid arthritis (RA) is an important public health problem because this disease often causes disability. RA is a chronic, destructive autoimmune disease characterized by joint infiltration by leucocytes, including T cells, B cells, macrophages and neutrophils, which leads to joint destruction and the development of extraarticular manifestations [1]. These infiltrating cells induce cartilage destruction and bone erosion through the increased synthesis of proinflammatory cytokines and chemokines [2][3][4].…”

Transcription Factor Assay of Peripheral Blood T cells in Different Groups of Rheumatoid Arthritis Patients

“…This destruction is responsible for working disability, physical dysfunction, O and a decline in the quality of life [3]. It is presumed that in RA disease, the synovial membrane is the main affected tissue, characterized by activation of fibroblastlike synoviocytes, the formation of pannus, as well as abnormal growth, and infiltration of inflammatory cells [4,5]. Also, one of the most prevalent chronic situations of joint damage is Osteoarthritis (OA) that breaks down the cartilage or cushion between joints that leads to pain, swelling, and problems when moving the joint [6].…”