THU671 Genes Encoding Adaptive Immune Receptor Repertoire Might Be Associated With The Risk Of Graves’ Disease And Antithyroid Drug-induced Agranulocytosis

Disclosure: C. Huang: None. S. Yang: None. S. Lai: None. H. Chen: None. P. Chen: None. Graves' disease (GD) is an autoimmune disorder characterized by the immune system attacking the thyroid gland cells, leading to hyperthyroidism. One serious adverse effect that can occur in GD patients receiving antithyroid drugs, such as thionamides, is antithyroid drug-induced agranulocytosis (TiA), which affects 0.1% to 0.4% of patients. While previous research has shown that specific human leukocyte antigen (HLA) genes/alleles are associated with GD or TiA, the role of the genes encoding adaptive immune receptor repertoire (gAIRR), including the B cell receptor and T cell receptor genes, in GD or TiA has not been explored. This study aims to investigate whether gAIRR has a genetic association with GD or TiA. We enrolled 128 GD patients, 19 TiA patients, and 104 controls, and conducted gAIRR genotyping using gAIRR Suite, a probe capture-based targeted sequencing and analysis platform. Our results identified several gAIRR alleles that were more prevalent in GD cases than in controls, including IGLV1-41*02N (a novel allele with the sequence closest to IGLV1-41*02, 20.3% in GD patients vs. 7.7% in controls, p=0.008), IGHV1-69*04N (12.5% vs. 3.8%, p=0.02), TRGV4*01 (46.9% vs. 31.7%, p=0.022), and several other alleles (such as TRBV6-6*03, IGKV1/OR22-5*01N, TRVB12-2*01N, TRAV8-4*01N, IGHV3-71*02, IGHV2-70*04N, etc.) We also found several gAIRR alleles that were less prevalent in GD cases than in controls, including IGLV5-45*03N, IGLV2-14*04, IGLV(V)-66*01, IGLV3-13*01N, TRBV20/OR9-2*02N, TRBD2*01, TRAV6*02, among others. Regarding the TiA cohort (compared to GD patients without TiA), some gAIRR alleles showed frequencies difference, but did not reach statistical significance. Overall, our findings provide supporting evidence that gAIRR genes/alleles might be associated with the development of GD or TiA. Future studies with larger sample sizes are necessary. Furthermore, a joint analysis of HLA and gAIRR genotypes might provide valuable insight into the pathogenesis of GD and TiA. Presentation: Thursday, June 15, 2023