Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome.

ABSTRACT

OBJECTIVE: Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients. METHODS: Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1-4, SCR 7, SCRs 11-14, and SCRs 19-20). Purified IgG from plasma from seven patients were used for functional analyses. RESULTS: All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19-20 domains of CFH but not the SCRs 1-4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells. CONCLUSIONS: Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.