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, Shinya Tasaki, Akihiko Yoshimura, Tsutomu Takeuchi

Research output: Contribution to journalArticle

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 (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), 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). 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. Trial registration: Not required.

Original languageEnglish
Article number153
JournalArthritis Research and Therapy
Volume22
Issue number1
DOIs
Publication statusPublished - 2020 Jun 22

Keywords

  • B cells
  • Gene co-expression network
  • Long non-coding RNA
  • Primary Sjögren's syndrome
  • Transcriptome

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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