Cutting edge: Autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-α in lupus patients in vivo

Silvia N. Kariuki, Kyriakos A. Kirou, Emma J. MacDermott, Lilliana Barillas-Arias, Mary K. Crow, Timothy B. Niewold

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

Increased IFN-α signaling is a primary pathogenic factor in systemic lupus erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN-αsignaling, and genetic variation of STAT4 has been associated with risk of SLE and rheumatoid arthritis. We measured serum IFN-α activity and simultaneous IFN-α-induced gene expression in PBMC in a large SLE cohort. The risk variant of STAT4 (T allele; rs7574865) was simultaneously associated with both lower serum IFN-α activity and greater IFN-α-induced gene expression in PBMC in SLE patients in vivo. Regression analyses confirmed that the risk allele of STAT4 was associated with increased sensitivity to IFN-αsignaling. The IFN regulatory factor 5 SLE risk genotype was associated with higher serum IFN-α activity; however, STAT4 showed dominant influence on the sensitivity of PBMC to serum IFN-α. These data provide biologic relevance for the risk variant of STAT4 in the IFN-α pathway in vivo.

Original languageEnglish (US)
Pages (from-to)34-38
Number of pages5
JournalJournal of Immunology
Volume182
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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