Application of T‐cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort‐study based on RA patients

Abstract

T‐cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti‐rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease‐modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.

Whole-Exome Sequencing and Analysis of the T Cell Receptor β and γ Repertoires in Rheumatoid Arthritis

“…Correlations between the TCR repertoire diversity and disease-related factors were also evaluated. The factors were negatively correlated with TCR diversity; this is in line with the result of a previous RA cohort study [ 27 ]. The DAS, SDAI, and CDAI scores were more strongly correlated with TCR diversity than the laboratory findings.…”

“…In general, the values of the Shannon–Weiner diversity index are usually between 1.5 and 3.5 and are known to be rare in excess of 4.5 [ 26 ]. However, in previous RA studies, the values of the Shannon–Wiener diversity indices were very high and exceeded 4.5 [ 25 , 27 ].…”

“…In the immune response, T cells and B cells are activated, resulting in an increase in inflammatory cytokines, production of matrix metalloproteinases, and induction and activation of osteoclasts; this results in bony destruction [ 3 ]. Because the aberrant expression of CD4+ T cells plays an important role in the pathogenesis of RA, the identification and quantitative comparison of CD4+ T cells are being studied in relation to the etiology of RA for early diagnosis and as a possible indicator of the disease course or response to treatment [ 27 ]. A previous study reported that the TCR repertoire helps in the early diagnosis of RA [ 18 ].…”

“…A previous study reported that the TCR repertoire helps in the early diagnosis of RA [ 18 ]. The TCR repertoire in patients with RA is known to be less diverse than in healthy individuals; this is related to the disease activity [ 25 , 27 ].…”