Abstract 13785: Profile and Characteristics of Peripheral T Cell Receptor Repertoires in Patients With Rheumatic Heart Disease Through High-Throughput Sequencing

Abstract

Introduction: Valve damage in rheumatic heart disease (RHD) is caused by immune cross-reaction to A streptococci attacking heart valve tissue of the host in which T cell is thought to play a key role. However, the immunological mechanism of is still poorly understood. The aim of the present study is to assess T cell receptor (TCR) repertoires in patients with RHD in comparison with healthy individuals. Hypothesis: T cells play a key role in regulating cell mediated immune response associated with heart valve damage in RHD. Methods: In the study, 21 subjects were enrolled, including 11 patients with RHD matching the diagnostic criteria of 2020 ACC/AHA guideline who accepted valve surgery, and 10 healthy individuals. The patient group had an average age of 52.5 years and 36.4% male. The healthy group had an average age of 37.1 years and 50% male. The TCR repertoires in all subjects were assessed by using high-throughput sequencing. Bio-informatics analysis was performed. Results: The overall immune characteristics of the patients and healthy individuals are obviously different. The TCR repertoire in the patients with RHD presented a significantly lower diversity than that in the healthy (D50-p<0.05) which implied that number of frequently expressed clonotypes were fewer in the patient group than that in the healthy group. The average fraction of the top 200 TCRs sequences was 20.95±8.89% in the patients which was significantly greater than that of 17.59±4.93% in healthy individuals (p<0.05), suggesting the TCR distribution in the patient group was more concentrated than in the healthy group. Heterogeneity of TCR repertoire was more pronounced in the patient group comparing to those in the healthy group (p<0.01). Both clonotype feature and TRBV-J combination feature of TCRs profile in the patient group demonstrated significant specificity for RHD(AUC>0.84, p< 0.05 and AUC>0.93, p< 0.05). Conclusions: TCR repertoires in patients with RHD is different from that in healthy individuals. The characteristics of TCR repertoires in patients with RHD indicated specific T cell response in the development of the disease,which provided clues to searching for biomarkers for early diagnosis of RHD and early blocking.