High-throughput T cell receptor sequencing reveals differential immune repertoires in autoimmune thyroid diseases

Abstract

BackgroundAutoimmune thyroid diseases (AITDs) are chronic autoimmune diseases specific to thyroid and mainly include Graves’ disease (GD) and Hashimoto’ thyroiditis (HT). The adaptive immunoreactivity of CD4+ T cells plays a crucial role in the pathogenesis of AITDs, but very little has been known about its changes in disease status. MethodsWe collected peripheral CD4+ T cells from 12 GD patients, including 6 newly diagnosed GD (NGD) and 6 refractory GD (RGD) patients, 6 HT patients and 6 healthy controls, and examined the gene expression profiles and colon types of T cells receptor (TCR) β chain complementarity determining region 3 (CDR3) using high-throughput sequencing. ResultsThe TCR repertoire were significantly expanded in AITDs groups, and some TCR genes were expressed more preferentially in AITDs group than in the healthy control group, including TRBV15 (P = 0.001), TRBV4-2 (P = 0.003), TRBV9 (P = 0.007), TRBV3-2 (P = 0.012), TRBV7-8 (P = 0.015), TRBV25-1 (P = 0.019), TRBV12-4 (P = 0.019) and TRBV27 (P = 0.02) in GD patients as well as TRBV29-1 (P = 0.004), TRBV12-4 (P = 0.004), TRBV6-5 (P = 0.011), TRBV7-2 (P = 0.012), TRBV27 (P = 0.012), TRBV9 (P = 0.031) and TRBV4-2 (P = 0.032) in HT patients. Moreover, subgroup analysis showed that the difference in the TCR spectrum between the normal group and NGD was not obvious, but a large number of differential genes appeared in the RGD group. ConclusionTCR spectrum has changed in patients with AITDs with expanded repertoire and many upregulated TRBV genes. Moreover, this difference is not apparent in GD patients at the initial stage, but as the disease progresses, the differences in TCR profiles became more pronounced.