Abstract
Abstract Autoantibodies and immune dysregulation are associated with systemic lupus erythematosus (SLE), but how these factors influence disease development is unknown. This study evaluates timing and changes in SLE-linked autoantibodies and soluble mediator pathways in the years preceding SLE classification. Serial sera from 84 SLE cases spanning pre- and post-SLE classification (average time = 5.98 years) and matched healthy controls (HC) were obtained from the Department of Defense Serum Repository. Adjusting for multiple comparison, a number of soluble mediators, including IL-5 (q=4.35×10−6), IL-6 (q=8.26×10−6), and IFN-γ (q=0.037), were significantly elevated in cases vs. HC >3.5 years pre-classification, prior to (IL-5 and IL-6) and concurrent with (IFN-γ) the earliest SLE-specific autoantibody specificity, anti-Ro/SSA. Th1-type, Th17-type, and TNF superfamily soluble mediators increased longitudinally in cases approaching SLE classification, but not in HC (q<0.05). In particular, serum levels of BLyS and APRIL were comparable in cases and HC until <10 months pre-classification (q=0.003 and q=0.019, respectively). Random forest models incorporating IL-5, IL-6, and IFN-γ levels (79–82% accuracy) distinguished future SLE patients better than models with ANA alone (58% accuracy) >3.5 years before classification. These data indicate that pre-clinical immune system perturbations allow for the accumulation of autoantibodies preceding clinical symptoms and SLE classification.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call