High-Throughput T Cell Receptor Sequencing Reveals Differential Immune Repertoires in Autoimmune Thyroid Disease

Abstract

Background: Autoimmune thyroid diseases (AITDs) are chronic autoimmune diseases specific to thyroid and mainly include Graves' diseases (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. Methods: We 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 of T cells receptor (TCR) β chain complementarity determining region 3 (CDR3) using high-throughput sequencing. Results: 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 of GD 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. Conclusion: TCR spectrum has changed in patients with AITDs with many genes being upregulated. 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. Funding: The present work was supported by grants from the Science and Technology Development Fund of Pudong New District Minsheng Scientific Research (Medical and Health) Project (No. PKJ2018-Y39) and the National Natural Science Foundation of China (Nos. 81873636 and 81670722). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: The study was approved by the Ethics Committee of Zhoupu Hospital. All subjects were informed of the present research project and signed written informed consent.