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

Jun Inamo, Katsuya Suzuki, Masaru Takeshita, Yoshiaki Kassai, Maiko Takiguchi, Rina Kurisu, Yuumi Okuzono, Shinya Tasaki, Akihiko Yoshimura, Tsutomu Takeuchi
2020 Arthritis Research & Therapy  
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. We 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+
more » ... ive B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD- (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA). 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. Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS. Not required.
doi:10.1186/s13075-020-02248-2 pmid:32571405 fatcat:7qeoebwp2ff4rdhmbz2tg3mkr4