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

BackgroundThe aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjogren's syndrome (pSS) at the transcriptome level.MethodsWe enrolled patients with pSS (n=6) and healthy controls (HCs) (n=6) in the discovery cohort using microarray and pSS (n=14) and HCs (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(+) (naive B cells), CD38(high)IgD(+) (pre-germinal centre B cells) and CD38IgD(-) (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA).ResultsExpression 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 IFN alpha. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.ConclusionOur transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.