OP0097 Autoantibodies Precede Interferon Elevation in Pre-Clinical Lupus. (10th June 2014)

• Record Type: Journal Article
• Authors: Munroe, M.E.; Fife, D.A.; Robertson, J.M.; Zhao, Y.D.; Bruner, B.F.; Niewold, T.B.; Tsokos, G.C.; Keith, M.P.; Harley, J.B.; James, J.A.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 98
• Page End: 98
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.3402
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Determining processes that lead to clinical illness in systemic lupus erythematosus (SLE) years before diagnosis would provide insight into the fundamental origins of SLE pathogenesis. Objectives: This study evaluates the temporal relationship between autoantibody production, interferon (IFN) levels and the onset of SLE. Methods: Serial sera from 56 pre-clinical SLE cases leading up to SLE classification (average timespan=4.3 years) and matched healthy controls were obtained from the Department of Defense Serum Repository. Sera samples were tested for autoantibodies (BioPlex2200), IFN-α activity, and soluble inflammatory mediators, including IFN associated chemokines and BLyS (B lymphocyte stimulator). Temporal relationships between IFN activity and autoantibody positivity were determined and confirmed using Path analysis. Results: Serum IFN-α activity scores, as well as IFN-correlated ( p<0.001 ) soluble mediators IFN-γ, IP-10, and BLyS levels increase in patients leading up to SLE disease classification ( p≤0.01 ). IFN activity positive individuals have an increased number of autoantibodies compared to IFN activity negative individuals ( p<0.05 ). Autoantibodies accumulate prior to or concurrent with increases in IFN activity in 84% of IFN positive cases. Of the 3 models of IFN vs. autoantibody positivity determined via Path analysis (autoantibody 1st, IFN activity 1st, or concurrent), autoantibody positivity prior to IFN activity ranked first, irrespective of whether DNA- or RNA-binding autoantibodies were present, as assessed by both Akaike's information criterion (AIC) and root mean square error of approximation (RMSEA). Conclusions: That autoantibodies accumulate prior to the increases in IFN activity levels suggests that the elevated IFN activity observed in SLE patients is a consequence of pre-clinical immune system perturbations. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.3402