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

T. B. Niewold, J. Hua, T. J.A. Lehman, J. B. Harley, M. K. Crow

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268 Scopus citations

Abstract

Interferon α (IFN-α) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-α 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-α activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-α 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-α activity, concordance in affected sib pairs and frequent transmission of the high IFN-α activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-α 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-α activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-α activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.

Original languageEnglish (US)
Pages (from-to)492-502
Number of pages11
JournalGenes and Immunity
Volume8
Issue number6
DOIs
StatePublished - Sep 1 2007

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ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

Cite this

Niewold, T. B., Hua, J., Lehman, T. J. A., Harley, J. B., & Crow, M. K. (2007). High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus. Genes and Immunity, 8(6), 492-502. https://doi.org/10.1038/sj.gene.6364408