SAT0429 Circulating Levels of IC3B and C3 Levels Correlate with Sledai-2K Responder Index-50 (S2K RI-50) Disease Activity Scores – the Castle (Complement Activation Signatures in Systemic Lupus Erythematosus) Study

BackgroundSystemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and complement activation, leading to protean manifestations with significant morbidity and mortality. A major unmet need in SLE is a biomarker that tracks with disease activity. One current approach is measuring complement activation by evaluating consumption of serum C3 and C4 components. As they are also acute phase reactants, production of C3 and C4 can balance consumption and serum levels may not decrease until late in a flare. iC3b is an inactive proteolytically derived molecule of C3b, with a short serum half-life (t1/2=30-90 minutes) (1). Increases in iC3b levels correlate with complement activation and the iC3b/C3 ratio is elevated when consumption exceeds production (2).ObjectivesTo correlate iC3b and C3 levels and elevated iC3b/C3 ratios with disease activity measured by S2K RI-50, anti-dsDNA Abs by ELISA, ESR and CRP.Methods82 adult SLE patients (89.0% female, age (mean ± SD): 41.4±12.9, S2K RI-50 score: 5.32±6.14) were enrolled from the Washington University Lupus Clinic. C3 was measured by nephelometry, and blood iC3b was assessed using the Kypha COMP ACT™ test, a lateral flow point of care assay. Analyses were restricted to the initial visit. Linear models analysis was used to generate predictive models of S2K RI-50 scores based on iC3b, C3, ESR, dsDNA,CRP levels and prednisone dose (≤7.5 mg/day versus >7.5 mg/day).ResultsBlood iC3b (P