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.
Highlights
Rheumatoid arthritis (RA) is a prevalent chronic systemic autoimmune disease that is characterized by severe synovial inflammation and pannus formation
We recruited eight RA patients who received different courses of biological DMARDs (bDMARDs) therapy—two receiving adalimumab (TNF-α inhibitor) only, three receiving adalimumab followed by rituximab, and three receiving adalimumab followed by tocilizumab—and all patients achieved sustained remission after treatment, with the Disease Activity Score of 28-joints (DAS28) less than 2.6 at the time of sample collection (Table 1; Figure 1)
Measurements of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which reflect the degree of inflammation and are basis of the DAS28 calculation, showed both indices being in normal ranges (ESR < 20, CRP < 1) in all patients after treatment
Summary
Rheumatoid arthritis (RA) is a prevalent chronic systemic autoimmune disease that is characterized by severe synovial inflammation and pannus formation. These processes eventually cause irreversible damage to the normal architecture of bone, cartilage, tendon, and ligament tissue, affecting the structure and function of the entire joint. Several genetic markers have been identified as risk factors. HLA DRB1 alleles are critical markers that have been reported in several populations [1, 2]. Dysregulation of T cells, B cells, antibodies, cytokines, osteoclasts, osteoblasts, amino acid citrullination, periodontal bacterial infection, and environmental factors, such as smoking and diet, are widely believed to be risk factors for rheumatoid arthritis [5, 6]
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