title: Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis.
abstract: Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system.
authors.affiliation: From the Nephrology Clinic, University Hospital "Tsaritsa Yoanna-ISUL," Medical University, 1527 Sofia, Bulgaria.
authors.forename: Vasil V
authors.initials: VV
authors.lastname: Vasilev
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Ecole Pratique des Hautes Études, 75014 Paris, France.
authors.forename: Remi
authors.initials: R
authors.lastname: Noe
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, and the Service d'Immunologie Biologique and.
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Dragon-Durey
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, and Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chauvet
authors.affiliation: From the Nephrology Clinic, University Hospital "Tsaritsa Yoanna-ISUL," Medical University, 1527 Sofia, Bulgaria.
authors.forename: Valentin J
authors.initials: VJ
authors.lastname: Lazarov
authors.affiliation: From the Nephrology Clinic, University Hospital "Tsaritsa Yoanna-ISUL," Medical University, 1527 Sofia, Bulgaria.
authors.forename: Boriana P
authors.initials: BP
authors.lastname: Deliyska
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, and the Service d'Immunologie Biologique and.
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, and.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, the Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, and lubka.roumenina@crc.jussieu.fr.
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D015331:Cohort Studies; D003176:Complement C3 / Q000276:immunology*; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D003176:Complement C3
keywords: antibody; autoimmune disease; complement system; protein-protein interaction; surface plasmon resonance (SPR)