title: Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura.
abstract: Acquired thrombotic thrombocytopenic purpura (TTP) has been linked to severe deficiency of ADAMTS-13 activity caused by autoantibodies inhibitory to ADAMTS-13. We report data on a patient with confirmed TTP who had severely reduced ADAMTS-13 activity but showed no ADAMTS-13 inhibition in a widely used fluid phase activity assay. With a newly developed enzyme-linked immunosorbent assay, using immobilized recombinant ADAMTS-13, we found high titers of IgM and IgG antibodies that bound to ADAMTS-13, but did not neutralize protease activity. These autoantibodies probably influenced the half-life of ADAMTS-13 or its binding to the endothelial cell surface, thereby compromising ADAMTS-13 activity in vivo. Given that ADAMTS-13 may interact physiologically with various receptors or ligands, the occurrence, distribution, and the epitope mapping of nonneutralizing antibodies will be an important area for future research.
authors.affiliation: Baxter BioScience, Biomedical Research Center, Uferstrasse 15, 2304 Orth/Donau, Austria. scheiff@baxter.com
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.forename: Paul
authors.initials: P
authors.lastname: Knöbl
authors.forename: Bettina
authors.initials: B
authors.lastname: Trattner
authors.forename: Barbara
authors.initials: B
authors.lastname: Plaimauer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mohr
authors.forename: Michael
authors.initials: M
authors.lastname: Dockal
authors.forename: Friedrich
authors.initials: F
authors.lastname: Dorner
authors.forename: Manfred
authors.initials: M
authors.lastname: Rieger
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008666:Metalloendopeptidases / Q000276:immunology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human