Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome

Abstract Background. The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level. Methods. We enrolled patients with pSS (n=6) and healthy controls (HC) (n=6) in the discovery cohort using microarray and pSS (n=14) and HC (n=12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38-IgD+ (Bm1), CD38+IgD+ (naïve B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD- (memory B cells). We performed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA).Results. Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.Conclusion. Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.