ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases

ADAMTS13 (a disintegrin-like and metallo-proteinase with thrombospondin type 1 motif), the metalloprotease that physiolog-ically 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 pa-tients with immunologic or thrombocyto-penic diseases different from TTP, using an enzyme-linked immunosorbent assay (ELISA). Immunoglobulin G (IgG) antibod-ies directed against ADAMTS13 were found in 97 % of untreated patients with acute acquired TMA who had plasma lev-els of ADAMTS13 activity below 10%. The corresponding prevalence of IgM antibod-ies was 11%. In contrast, anti-ADAMTS13 antibodies of G or M isotypes were de-tected 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 erythem-atosus (SLE; n 40), and the antiphos-pholipid 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 antibod-ies in these groups is unclear. In conclu-sion, the ELISA method detected anti-ADAMTS13 IgG antibodies in a very large proportion of patients with acquired TMA associated with severe ADAMTS13 defi-ciency, and was more sensitive than the inhibitor assay. (Blood. 2005;106:1262-1267) © 2005 by The American Society of Hematolog