Characterization of the prevalence, functional consequences and disease associations of autoantibodies against the positive complement regulator properdin in patients with lupus nephritis P­18­009 G. MihaylovaI, V. Vasilev *II, D. Ivanova *III, M. Daugan *IV , R. Noe *IV , M. Dragon­Durey *IV , L. Roumenina *IV , M.R. Radanova *III IMedical University “Prof. Dr. Paraskev Stoyanov”, Varna, Varna, Bulgaria, IIClinics of Nephrology, University Hospital ­ “Tzaritza Ioanna – ISUL”, Medical University of Sofia, Sofia, Bulgaria, Sofia, Bulgaria, IIIDepartment of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, Varna, Bulgaria, Varna, Bulgaria, IV Cordeliers Research Center, Complement and diseases team, INSERM UMRS 1138, Paris, France, Paris, France Lupus nephritis (LN) is a common major organ manifestation of the Systemic lupus erythematosus (SLE). Complement is a key player in disease pathogenesis. It can be deregulated by autoantibodies (Abs), predisposing thus to renal injury. We screened for Abs against the components of the classical and alternative complement pathways by ELISA and identified previously unrecognized reactivity against the only positive regulator – properdin (factor P, FP) in 70.27%(52/74) of the patients with LN and 1.33% (1/75) healthy controls. The interaction of purified IgG from these patients with FP was confirmed using surface plasmon resonance. The presence of anti­FP Abs significantly correlated with immunological markers of LN activity – ANA, anti­dsDNA and low levels of C3. Anti­FP Abs levels were significantly associated with renal histologic lesions, like endocapillary proliferation, glomerular leukocyte infiltration and glomerular sclerosis. High levels of these Abs correlated also with histological activity index. Combination of anti­FP and anti­C1q may enhance the specificity in the identification of patients with active, class IV and the most severe LN (class A according to BILAG Renal score). The clinical relevance of the anti­FP Abs could be explained by their capacity to potentiate the activity of the alternative pathway. We incubated apoptotic cells with human serum in alternative pathway condition (EGTA­Mg) +/­ IgG from anti­FP positive LN patients. C3 fragments’ deposits were enhanced in presence of anti­FP positive IgG, compared to IgG from healthy donors, measured by flow cytometry. This was not related to increased FP binding to the cells, but rather to a direct effect on the convertase. Therefore, anti­FP Abs have clear functional consequences, which may contribute to disease severity. * The authors marked with an asterisk equally contributed to the work..