title: Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN.
abstract: In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9.In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.
authors.affiliation: Team Complement and Diseases Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1138, Paris, France.|Assistance Publique-Hôpitaux de Paris, Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Marinozzi
authors.affiliation: Team Complement and Diseases Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1138, Paris, France.|Université Paris Descartes Sorbonne Paris-Cité, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
authors.affiliation: Team Complement and Diseases Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1138, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chauvet
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Néphrologie et de Transplantation rénale, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.affiliation: Service de Néphrologie et de Transplantation rénale, Hôpital Bois Guillaume, Rouen, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bertrand
authors.affiliation: Service de Néphrologie et de Transplantation rénale, Strasbourg, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Olagne
authors.affiliation: Service de Néphrologie et de Transplantation rénale, Lille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Frimat
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Néphrologie, Hôpital Trousseau, Paris, France.
authors.forename: Tim
authors.initials: T
authors.lastname: Ulinski
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Néphrologie et de Transplantation rénale, Hôpital Robert Debré, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.affiliation: Aix Marseille université, Assistance publique-Hôpitaux de Marseille, Service de Néphrologie et de Transplantation rénale, Marseille, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Burtey
authors.affiliation: Service de Néphrologie et Transplantation rénale, Hopital Foch, Paris, France; and.
authors.forename: Michel
authors.initials: M
authors.lastname: Delahousse
authors.affiliation: Service de Néphrologie et de Transplantation rénale, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Néphrologie et de Transplantation rénale, Hôpital Necker, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Team Complement and Diseases Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1138, Paris, France; veronique.fremeaux-bacchi@aphp.fr moglie.lequintrec@gmail.com.|Assistance Publique-Hôpitaux de Paris, Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.affiliation: Team Complement and Diseases Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1138, Paris, France; veronique.fremeaux-bacchi@aphp.fr moglie.lequintrec@gmail.com.|Service de Néphrologie et Transplantation rénale, Hopital Foch, Paris, France; and.
authors.forename: Moglie
authors.initials: M
authors.lastname: Le Quintrec
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D003179:Complement C3b / Q000276:immunology*; D011415:Complement Factor B / Q000276:immunology*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D003179:Complement C3b; D011415:Complement Factor B
keywords: chronic glomerulonephritis; clinical immunology; complement