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

Abstract

This study investigated the potential genetic variants of rheumatoid arthritis (RA) using whole-exome sequencing (WES) and evaluated the disease course using T cell receptor (TCR) repertoire analysis. Fourteen patients with RA and five healthy controls (HCs) were enrolled. For the RA patient group, only treatment-naïve patients were recruited, and data were collected at baseline as well as at 6 and 12 months following the initiation of the disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using the Shannon–Wiener diversity index. While some variants were detected by WES, their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in the RA group was lower than that in the HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively correlated with the laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified, and the clinical significance of the TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Keywords

• whole-exome sequencing
• T cell receptor repertoire
• diversity
• rheumatoid arthritis