Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus

Arthritis Rheum. 2004 Dec;50(12):3958-67. doi: 10.1002/art.20798.

Abstract

Objective: To study the contribution of interferon-alpha (IFNalpha) and IFNgamma to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).

Methods: Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNalpha and IFNgamma. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs.

Results: Expression of IFNalpha-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNalpha pathway activation correlated highly with the inherent responsiveness of those genes to IFNalpha, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNgamma was not significantly increased in SLE PBMCs compared with control PBMCs. IFNalpha-regulated gene-inducing activity was detected in some SLE plasma samples.

Conclusion: The coordinate activation of IFNalpha-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNalpha is the predominant stimulus for IFIG expression in lupus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cohort Studies
  • Gene Expression Regulation*
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / genetics*
  • Interferon-alpha / pharmacology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics*
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Carrier Proteins
  • IFIT1 protein, human
  • Interferon-alpha
  • RNA, Messenger
  • Interferon-gamma