Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus.

Abstract

The transmembrane endoplasmic reticulum (ER) protein UNC93B plays an essential role in the normal response to signalling through intracellular Toll-like receptor (TLR)3, TLR7, TLR8 and TLR9. In the current study, we examined the level of UNC93B expression on peripheral B cells from patients with active SLE, and investigated any correlation with SLE pathogenesis. Peripheral blood mononuclear cells (PBMCs) and B cells from 43 active SLE patients were analysed by quantitative RT-PCR to determine the precise levels of UNC93B mRNA. We also analysed UNC93B protein expression on B cells from SLE patients using immunoblotting. The expression of UNC93B mRNA on PBMCs from active SLE patients was significantly higher than that of controls (P < 0.05). The intracellular expression level of UNC93B protein on CD20(+) B cells from active SLE patients was also higher than in the controls. Moreover, the expression of UNC93B on B cells from lupus patients correlated significantly with high titres of anti-dsDNA antibody (P < 0.05). Up-regulation of the ER membrane protein UNC93B on human lupus B cells suggests that TLR9 and UNC93B play a partial role in the pathogenesis of SLE by inducing defective peripheral B-cell tolerance.