Endocrine Abstracts

Background: Graves’ disease (GD) is a common autoimmune disorder characterized by the production of autoantibodies targeting the thyroid, leading to hypothyroidism. It is widely accepted that B lymphocytes play a significant role in GD as they are the source of autoantibodies (TRAb) against the thyroid-stimulating hormone receptor (TSHR). Previously, we reported that B cells infiltrate the thyroid tissue of GD patients, and in this study we observed that the percentage of peripheral blood B cells of GD patients was significantly higher than that in healthy controls. However, few studies have sought to understand the role of thyroid antigen-reactive B cells during disease development.

Methods: LncRNA and mRNA microarray expression profiling were performed to identify the differentially expressed genes in purified CD19⁺B cells. Go and Pathway analysis showed the potential function and pathway involved in the target genes. Two independent algorithms were used to predict the lncRNAs that regulate target gene. The Protein-protein interaction (PPI) network present the underlying interaction of these differential genes.

Results: 410 differentially expressed mRNAs between GD patients and controls, with 79 mRNAs being upregulated and 331 being downregulated in the B lymphocytes of GD patients as compared with controls. Quantitative real-time polymerase chain reaction (qRT-PCR) validated T-cell leukemia/lymphoma-1A (TCL1A) and SH2 domain containing 1A (SH2D1A), were upregulated and downregulated, respectively, in GD patients as compared to controls. GO and Pathway analyses revealed that TCL1A and SH2D1A genes are highly involved in B cell proliferation and survival. lncRNAs TC14001829.hg.1 and TC14002143.hg.1 are predicted to regulate TCL1A and lncRNA TC0X002222.hg.1 to regulate SH2D1A. qRT-PCR validated the upregulation of the lncRNAs TC14001829.hg.1 and TC14002143.hg.1, and the downregulation of the lncRNA TC0X002222.hg.1 in GD patients.

Conclusion: In conclusion, our study determined the expression profiles of mRNA and lncRNA in B cells of GD patients, and highlighted the changes in TCL1A, SH2D1A, and the related lncRNAs TC14002143.hg.1, TC14001829.hg.1, and TC0X00222.hg.1, which may participate in GD development by modulating B cell proliferation and survival. These genes and lncRNA could represent novel biomarkers and therapeutic targets for GD.