Microarray profile of B cells from Graves’ disease patients reveals biomarkers of proliferation

Abstract

B lymphocytes are the source of autoantibodies against the thyroid-stimulating hormone receptor (TSHR) in Graves’ disease (GD). Characterization of au toimmune B-cell expression profiles might enable a better understanding of GD pathogenesis. To reveal this, the expression levels of long noncoding RNAs (lncRNAs) and mRNAs (g enes) in purified B cells from patients with newly diagnosed GD and healthy individuals w ere compared using microarrays, which elucidated 604 differentially expressed lncRNAs (DE-lncRNAs) and 410 differentially expressed genes (DEGs). GO and pathway analyses r evealed that the DEGs are mainly involved in immune response. A protein–protein inter action network presented experimentally validated interactions among the DEGs. Two indep endent algorithms were used to identify the DE-lncRNAs that regulate the DEGs. Fu nctional annotation of the deregulated lncRNA–mRNA pairs identified 14 pairs with mR NAs involved in cell proliferation. The lncRNAs TCONS_00022357-XLOC_010919 and n335641 were predicted to regulate TCL1 family AKT coactivator A (TCL1A), and the lncRNA n337845 was predicted to regulate SH2 domain containing 1A (SH2D1A). TCL1A and SH2D1A are highly involved in B-cell proliferation. The differential expression of both genes was validated by qRT-PCR. In conclusion, lncRNA and mRNA expression profiles of B cells fr om patients with GD indicated that the lncRNA–mRNA pairs n335641–TCL1A, TCONS_00022357-XLOC_010919– TCL1A, and n337845–SH2D1A may participate in GD pathogenesis by modulating B-cell proliferation and survival. Therefore, the identified lncRNA and mRNA may represent novel biomarkers and therapeutic targets for GD.

Keywords

• graves’ disease
• b cells
• microarray
• lncrna
• mrna