title: ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases.
abstract: Autoantibodies neutralizing human ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif), the metalloprotease that physiologically cleaves von Willebrand factor, are a major cause of severe deficiency of the protease and of acquired thrombotic thrombocytopenic purpura (TTP). We evaluated prevalence of anti-ADAMTS13 antibodies in 59 patients with thrombotic microangiopathies (TMAs) and in 160 patients with immunologic or thrombocytopenic diseases different from TTP, using an enzyme-linked immunosorbent assay (ELISA). Immunoglobulin G (IgG) antibodies directed against ADAMTS13 were found in 97% of untreated patients with acute acquired TMA who had plasma levels of ADAMTS13 activity below 10%. The corresponding prevalence of IgM antibodies was 11%. In contrast, anti-ADAMTS13 antibodies of G or M isotypes were detected in 20% of patients with TMA with ADAMTS13 activity above 10%. The ELISA was more sensitive than the standard functional inhibitor assay for detecting antibodies against ADAMTS13. Patients with thrombocytopenia from various causes (n = 50), systemic lupus erythematosus (SLE; n = 40), and the antiphospholipid antibody syndrome (APS; n = 55) had prevalences of IgG antibodies of 8%, 13%, and 5% respectively, only slightly higher than the prevalence in 111 healthy donors (4%). A rather high prevalence of anti-ADAMTS13 IgM antibodies was found in patients with SLE and APS (18% each). The clinical significance of IgM antibodies in these groups is unclear. In conclusion, the ELISA method detected anti-ADAMTS13 IgG antibodies in a very large proportion of patients with acquired TMA associated with severe ADAMTS13 deficiency, and was more sensitive than the inhibitor assay.
authors.affiliation: Baxter BioScience, Biomedical Reserach Center, Orth, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rieger
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Andrea
authors.initials: A
authors.lastname: Herzog
authors.forename: Gabi
authors.initials: G
authors.lastname: Gerstenbauer
authors.forename: Christian
authors.initials: C
authors.lastname: Konetschny
authors.forename: Klaus
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Inge
authors.initials: I
authors.lastname: Scharrer
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.forename: Miriam
authors.initials: M
authors.lastname: Galbusera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Martina
authors.initials: M
authors.lastname: Böhm
authors.forename: Barbara
authors.initials: B
authors.lastname: Plaimauer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D016736:Antiphospholipid Syndrome / Q000150:complications; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008666:Metalloendopeptidases / Q000276:immunology*; D015995:Prevalence; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology*; D013921:Thrombocytopenia / 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