Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

• DOI: 10.1681/asn.2016030343
• Publication Date: 2017-01-18T02:10:46Z
• Authors: Maria Chiara Mari...; Lubka T. Roumenina; Sophie Chauvet; Alexandre Hertig; Dominique Bertrand; Jérome Olagne; Marie Frimat; Tim Ulinski; Georges Deschênes; Stephane Burtey; Michel Delahousse; Bruno Moulin; Christophe Legendre; Véronique Frémeau...; Moglie Le Quintrec
• Keywords: Membranoproliferative glomerulonephritis; C3-convertase; Complement factor B; Glomerulopathy

In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort 141 C3G Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB anti-C3b using ELISA. identified seven IgG, five IgG. Of these 15 patients, ten were diagnosed Ig-MPGN. Among those available data, 92% had nephrotic syndrome, 64% AKI, 67% documented infection. Patients negative much lower rates infection (17 [25%] one [10%] patient Ig-MPGN). After 48 months, four (26%) positive developed ESRD or died. All high plasma Bb levels, six (40%) low levels C3, nine (60%) soluble C5b9. vitro, purified from Abs selectively enhanced activity; anti-C3b/anti-FB C5 cleavage. stabilized C3bBb perturbed C3b binding to receptor 1 but did not perturb factor H. conclusion, prevalence activation similar Ig-MPGN C3G, suggesting pathogenic mechanisms. Identification underlying defect could lead improved treatment.