Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases.

Autor:	Blanc C; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Université Paris Diderot, 75013 Paris, France;, Togarsimalemath SK; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Service de Néphrologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75970 Paris Cedex 20, France;, Chauvet S; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Université Paris Descartes, 75006 Paris, France;, Le Quintrec M; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Service de Néphrologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75970 Paris Cedex 20, France;, Moulin B; Service de Néphrologie et Transplantation Rénale, Centre Hospitalier Universitaire Hautepierre, 67098 Strasbourg, France;, Buchler M; Service de Néphrologie, Immunologie Clinique, Hôpital Bretonneau, 37044 Tours, France;, Jokiranta TS; Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland; and., Roumenina LT; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France;, Fremeaux-Bacchi V; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75908 Paris, France., Dragon-Durey MA; INSERM Unité Mixte de Recherche S1138, 'Complément et Maladies' Équipe 10, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 75006 Paris, France; Service de Néphrologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75970 Paris Cedex 20, France; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75908 Paris, France marie-agnes.durey@egp.aphp.fr.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Jun 01; Vol. 194 (11), pp. 5129-38. Date of Electronic Publication: 2015 Apr 27.
DOI:	10.4049/jimmunol.1402770
Abstrakt:	Autoantibodies targeting factor H (FH), which is a main alternative complement pathway regulatory protein, have been well characterized in atypical hemolytic uremic syndrome (aHUS) but have been less well described in association with alternative pathway-mediated glomerulopathies (GP). In this study, we studied 17 patients presenting with GP who were positive for anti-FH IgG. Clinical data were collected and biological characteristics were compared with those of patients presenting with anti-FH Ab-associated aHUS. In contrast to the aHUS patients, the GP patients had no circulating FH-containing immune complexes, and their anti-FH IgG had a weaker affinity for FH. Functional studies demonstrated that these Abs induced no perturbations in FH cell surface protection or the binding of FH to its ligand. However, anti-FH IgG samples isolated from three patients were able to affect the factor I cofactor activity of FH. Epitope mapping identified the N-terminal domain of FH as the major binding site for GP patient IgG. No homozygous deletions of the CFHR1 and CFHR3 genes, which are frequently associated with the anti-FH Ab in aHUS patients, were found in the GP patients. Finally, anti-FH Abs were frequently associated with the presence of C3 nephritic factor in child GP patients and with monoclonal gammopathy in adult GP patients, who frequently showed Ig Lchain restriction during reactivity against factor H. These data provide deeper insights into the pathophysiological differences between aHUS and GP, demonstrating heterogeneity of anti-FH IgG. (Copyright © 2015 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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