High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus

Genes Immun. 2007 Sep;8(6):492-502. doi: 10.1038/sj.gene.6364408. Epub 2007 Jun 21.

Abstract

Interferon alpha (IFN-alpha) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-alpha activity is a cause or a result of the disease. We studied 266 SLE patients and 405 of their healthy relatives, and frequently found high serum IFN-alpha activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-alpha activity was clustered in specific families in both SLE patients and their healthy first-degree relatives, suggesting a heritable trait. Heritability was also supported by quantitative familial correlation of IFN-alpha activity, concordance in affected sib pairs and frequent transmission of the high IFN-alpha activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-alpha activity in SLE patients; however these autoantibodies were very uncommon in healthy family members and did not explain the observed familial correlations. The frequency of high IFN-alpha activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-alpha activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / immunology
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Case-Control Studies
  • Cell Line
  • Female
  • Humans
  • Interferon-alpha / blood*
  • Interferon-alpha / genetics*
  • Interferon-alpha / immunology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • RNA-Binding Proteins / immunology
  • Risk Factors

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Interferon-alpha
  • RNA-Binding Proteins