Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway

Brandon W. Higgs, Zheng Liu, Barbara White, Wei Zhu, Wendy I. White, Chris Morehouse, Philip Brohawn, Peter A. Kiener, Laura Richman, David Fiorentino, Steven A. Greenberg, Bahija Jallal, Yihong Yao

Research output: Contribution to journalArticle

Abstract

Objective: To characterise activation of the type I interferon (IFN) pathway in patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA) and systemic scleroderma (SSc) and to evaluate the potential to develop a molecular diagnostic tool from the peripheral blood that refl ects this activation in disease-affected tissues. Methods: Overexpressed transcripts were identifi ed in the whole blood (WB) of 262 patients with SLE, 44 with DM, 33 with PM, 28 with SSc and 89 with RA and compared with 24 healthy subjects using Affymetrix microarrays. A fi ve gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements. Results: A common set of 36 type I IFN inducible transcripts were identifi ed among the most overexpressed in the WB of all subjects. Signifi cant activation of the type I IFN pathway in subgroups of each of the fi ve diseases studied was observed. Baseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects with SLE, PM and SSc, as did various serum autoantibody levels in subjects with SLE and DM. This signature was also well correlated between disease-affected tissue and WB in subjects with SLE, DM, PM and SSc. Conclusions: The results indicate that the type I IFN pathway is activated in patient subsets of fi ve rheumatic diseases and suggest that these subsets may benefit from anti-IFN therapy.

Original languageEnglish (US)
Pages (from-to)2029-2036
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

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    Higgs, B. W., Liu, Z., White, B., Zhu, W., White, W. I., Morehouse, C., Brohawn, P., Kiener, P. A., Richman, L., Fiorentino, D., Greenberg, S. A., Jallal, B., & Yao, Y. (2011). Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway. Annals of the Rheumatic Diseases, 70(11), 2029-2036. https://doi.org/10.1136/ard.2011.150326