title: Anti-complement-factor H-associated glomerulopathies.
abstract: Atypical haemolytic uraemic syndrome (aHUS), an important cause of acute kidney injury, is characterized by dysregulation of the complement pathway, frequent need for dialysis, and progression to end-stage renal disease. Autoantibodies against complement factor H (FH), the main plasma regulatory protein of the alternative pathway of the complement system, account for a considerable proportion of children with aHUS. The autoantibodies are usually associated with the occurrence of a homozygous deletion in the genes encoding the FH-related proteins FHR1 and FHR3. High levels of autoantibodies, noted at the onset of disease and during relapses, induce functional deficiency of FH, whereas their decline, in response to plasma exchanges and/or immunosuppressive therapy, is associated with disease remission. Management with plasma exchange and immunosuppression is remarkably effective in inducing and maintaining remission in aHUS associated with FH autoantibodies, whereas terminal complement blockade with eculizumab is considered the most effective therapy in other forms of aHUS. Anti-FH autoantibodies are also detected in a small proportion of patients with C3 glomerulopathies, which are characterized by chronic glomerular injury mediated by activation of the alternative complement pathway and predominant C3 deposits on renal histology.
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 15 rue de l'ecole de medecine, 75006 Paris, France.|Université Paris Descartes, Paris, France.|Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, APHP, 20 rue Leblanc, 75015 Paris, France.
authors.forename: Marie-Agnes Dragon
authors.initials: MA
authors.lastname: Durey
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, 15 rue de l'ecole de medecine, 75006 Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: Shambhuprasad Kotresh
authors.initials: SK
authors.lastname: Togarsimalemath
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Bagga
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome / Q000276:immunology* / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D017242:Complement Factor H / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology* / Q000628:therapy; D006801:Humans
chemical_list: D001323:Autoantibodies; C493495:CFH protein, human; D003176:Complement C3; D017242:Complement Factor H