B-215 Use of Whole Exome Sequencing and T Cell Receptor β Repertoires Analysis for Identifying Potential Genetic Variants in Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, which is reported to affect about approximately 1% of the adult population worldwide. And, it is associated with progressive disease courses, systemic complications, early mortality, and a high socioeconomic burden. The pathogenesis of RA is too complex to be fully understood yet, but abnormal and pathogenic T-cell responses that evade normal immune functions could be considered one of the mechanisms of RA development. Herein, we used whole exome sequencing (WES) and T cell receptor/T cell receptor β repertoires analysis (TCR/TRB) to identify the potential genetic variants in RA. Methods Peripheral blood samples from 18 RA patients and 5 healthy controls were analyzed. For RA patients, the baseline naïve samples were collected before disease-modifying anti-rheumatic drugs treatment was started, and both WES and TRB were tested. After 6 months and 12 months of treatment initiation, additional samples were collected and TRB was tested. A total of 18 WES and 27 TRB tests were conducted. WES was done on the MGI-G400 platform (MGI Tech Co., Ltd., Shenzhen, China) and TCR/TRB was done using the LymphoTrack TCR/TRB assay (Invivoscribe Technologies, San Diego, CA, USA) on the MiSeq system (Illumina Inc, San Diego, CA, USA). Results In RA patients, deleterious variants that have been reported to be relevant in various diseases were identified in a total of 217 genes. Among 18 RA patients, 5 (27.8%) patients had variants that were suspected to be associated with the pathogenesis of RA, including JAK3, PADI4, TNFSF18, TRAF1, NFKB, etc. Of the 27 TCR/TRB tests, 10 TCR (37.0%) and 14 TRB (51.9%) results had significant changes in RA patients. Conclusion The aim of this study is to provide clinical evidence for developing diagnostic and/or prognostic markers for RA. Further analysis whether these variants found in this study are clinically significant and valuable as markers in RA. In addition, it is expected that the results of our study will be used as basic data applied to other rheumatoid diseases such as systemic lupus erythematosus and Bechet’s disease.