title: Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation.
abstract: Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-α in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-α2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-α2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients (n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls (n = 27). IFN-α2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity (p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-α2 (median one, range 3; p < 0.001). Solution phase micro-bead assay thus identified increased IFN-α2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-α2 in disease perpetuation in a large subset of SLE patients.
authors.affiliation: Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Becker-Merok
authors.forename: G
authors.initials: G
authors.lastname: Østli-Eilersten
authors.forename: S
authors.initials: S
authors.lastname: Lester
authors.forename: Jc
authors.initials: J
authors.lastname: Nossent
mesh_terms: D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D016898:Interferon-alpha