title: Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome.
abstract: The autoimmune form of atypical hemolytic uremic syndrome (HUS) is characterized by circulating autoantibodies against the complement regulator factor H, and is often associated with deficiency of the factor H-related proteins CFHR1 and CFHR3. Here we studied whether anti-factor H autoantibodies crossreact with CFHR1, and determined functional consequences of this. In ELISA, anti-factor H immunoglobulin G (IgG) autoantibodies from 24 atypical HUS patients bound to the short consensus repeat 20 domain of factor H, 21 antibodies also recognized CFHR1, but none CFHR3. Three patients also had anti-factor H IgA autoantibodies crossreacting with CFHR1. Analysis of the IgG fractions in CFHR1-deficient patients found that CFHR1-IgG complexes were formed during plasma exchange treatment, indicating that autoantibodies recognize CFHR1 in vivo. Recombinant CFHR1 prevented hemolysis of sheep erythrocytes caused by patient plasma containing anti-factor H IgG, but it did not inhibit red cell lysis caused by a factor H mutation (W1183 L) in the short consensus repeat 20 domain. Thus, exogenous CFHR1 provided during plasma exchange therapy may neutralize anti-factor H autoantibodies and help in the treatment of autoimmune atypical HUS.
authors.affiliation: Junior Research Group Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Strobel
authors.forename: Cynthia
authors.initials: C
authors.lastname: Abarrategui-Garrido
authors.forename: Elena
authors.initials: E
authors.lastname: Fariza-Requejo
authors.forename: Harald
authors.initials: H
authors.lastname: Seeberger
authors.forename: Pilar
authors.initials: P
authors.lastname: Sánchez-Corral
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D065766:Atypical Hemolytic Uremic Syndrome; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000235:genetics; D015551:Autoimmunity; D001798:Blood Proteins / Q000276:immunology; D016022:Case-Control Studies; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000276:immunology*; D017242:Complement Factor H / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005858:Germany; D006461:Hemolysis; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D009154:Mutation; D010951:Plasma Exchange; D012756:Sheep; D013030:Spain
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D007074:Immunoglobulin G; D017242:Complement Factor H