ARID3a gene profiles are strongly associated with human interferon alpha production

J Autoimmun. 2019 Jan;96:158-167. doi: 10.1016/j.jaut.2018.09.013. Epub 2018 Oct 5.

Abstract

Type I interferons (IFN) causes inflammatory responses to pathogens, and can be elevated in autoimmune diseases such as systemic lupus erythematosus (SLE). We previously reported unexpected associations of increased numbers of B lymphocytes expressing the DNA-binding protein ARID3a with both IFN alpha (IFNα) expression and increased disease activity in SLE. Here, we determined that IFNα producing low density neutrophils (LDNs) and plasmacytoid dendritic cells (pDCs) from SLE patients exhibit strong associations between ARID3a protein expression and IFNα production. Moreover, SLE disease activity indices correlate most strongly with percentages of ARID3a+ LDNs, but were also associated, less significantly, with IFNα expression in LDNs and pDCs. Hierarchical clustering and transcriptome analyses of LDNs and pDCs revealed SLE patients with low ARID3a expression cluster with healthy controls and identified gene profiles associated with increased proportions of ARID3a- and IFNα-expressing cells of each type. These data identify ARID3a as a potential transcription regulator of IFNα-related inflammatory responses and other pathways important for SLE disease activity.

Keywords: ARID3a; Interferon alpha; Low density neutrophils; Lupus; Plasmacytoid dendritic cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / physiology*
  • DNA-Binding Proteins / genetics*
  • Dendritic Cells / physiology*
  • Disease Progression
  • Female
  • Gene Expression Regulation
  • Genetic Association Studies
  • Humans
  • Immunity, Innate
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism*
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Neutrophils / physiology*
  • Severity of Illness Index
  • Transcription Factors / genetics*
  • Transcriptome

Substances

  • ARID3A protein, human
  • DNA-Binding Proteins
  • Interferon-alpha
  • Transcription Factors