Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome

Józsi, Mihály and Strobel, S. and Dahse, H. M. and Liu, W. S. and Hoyer, P. F. (2007) Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. BLOOD, 110 (5). pp. 1516-1518. ISSN 0006-4971


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The atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. In addition to mutations in complement regulators, factor H (FH)-specific autoantibodies have been reported for aHUS patients. The aim of the present study was to understand the role of these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from 5 unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all 5 autoantibodies, the binding site was localized to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH binding to C3b. In addition, autoantibody-positive patients' plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS-associated FH autoantibodies mimic the effect of C-terminal FH mutations, as they inhibit the regulatory function of FH at cell surfaces by blocking its C-terminal recognition region.

Item Type: Article
Uncontrolled Keywords: SHEEP; Recombinant Proteins/chemistry/immunology; Protein Structure, Tertiary/genetics; Protein Binding/genetics/immunology; Peptide Mapping; Mutation/immunology; Molecular Mimicry/genetics/*immunology; Male; Immunoglobulin G/genetics/immunology; Humans; Hemolytic-Uremic Syndrome/genetics/*immunology/pathology; Hemolysis/immunology; Genetic Diseases, Inborn/genetics/immunology/pathology; Female; Erythrocytes/chemistry/immunology; Complement Factor H/genetics/*immunology; Complement C3b/genetics/immunology; Complement Activation/genetics/*immunology; Child, Preschool; Child; Binding Sites, Antibody/genetics/*immunology; Autoimmune Diseases/genetics/*immunology/pathology; Autoantibodies/chemistry/*immunology; Animals
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 31 Aug 2017 14:25
Last Modified: 31 Aug 2017 14:25

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