Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity

Clin Rheumatol. 2018 Oct;37(10):2675-2684. doi: 10.1007/s10067-018-4138-7. Epub 2018 May 17.

Abstract

Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells. Flow cytometry was used to measure the IFN-γ levels in lymphocytes. The mRNA levels of type II IFN-inducible genes, IFNG, TBX21, and EOMES were significantly higher in SLE patients than those in HDs. Similarly, the percentages of IFN-γ-producing cells in lymphocytes and their subsets in SLE patients were significantly increased. Linear regression indicated that IFNG expression levels and type II IFN scores were positively correlated with anti-double-stranded DNA autoantibody levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. Compared with patients with low type I IFN scores, patients with high type I IFN scores showed increased type II IFN scores and SLEDAI scores. Type II IFN scores were positively associated with type I IFN scores. The IFN-γ signaling pathway is activated in SLE patients and may be considered an index of disease activity. IFN-γ, together with type I IFNs, promotes the pathogenesis of SLE.

Keywords: Disease activity; EOMES; Interferon-gamma; Interferon-inducible genes; Systemic lupus erythematosus; TBX21.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Chemokine CXCL10 / blood
  • Chemokine CXCL9 / blood
  • Child
  • China
  • Complement C1 Inhibitor Protein / metabolism
  • Female
  • GTP-Binding Proteins / blood
  • Humans
  • Interferon Regulatory Factor-1 / blood
  • Interferon Type I / blood*
  • Interferon-gamma / blood*
  • Leukocytes, Mononuclear / chemistry*
  • Lupus Erythematosus, Systemic / blood*
  • Male
  • Middle Aged
  • RNA, Messenger / blood
  • Signal Transduction
  • T-Box Domain Proteins / blood
  • Young Adult

Substances

  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Complement C1 Inhibitor Protein
  • EOMES protein, human
  • GBP1 protein, human
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Type I
  • RNA, Messenger
  • SERPING1 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma
  • GTP-Binding Proteins