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

研究成果: Article査読

4 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号153
ジャーナルArthritis Research and Therapy
22
1
DOI
出版ステータスPublished - 2020 6 22

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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