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.
| Original language | English |
|---|---|
| Pages (from-to) | 1262-1267 |
| Number of pages | 6 |
| Journal | Blood |
| Volume | 106 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Aug 15 2005 |
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ASJC Scopus subject areas
- Hematology
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ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. / Rieger, Manfred; Mannucci, Pier Mannuccio; Kremer Hovinga, Johanna A.; Herzog, Andrea; Gerstenbauer, Gabi; Konetschny, Christian; Zimmermann, Klaus; Scharrer, Inge; Peyvandi, Flora; Galbusera, Miriam; Remuzzi, Giuseppe; Böhm, Martina; Plaimauer, Barbara; Lämmle, Bernhard; Scheiflinger, Friedrich.
In: Blood, Vol. 106, No. 4, 15.08.2005, p. 1262-1267.Research output: Contribution to journal › Article
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TY - JOUR
T1 - ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases
AU - Rieger, Manfred
AU - Mannucci, Pier Mannuccio
AU - Kremer Hovinga, Johanna A.
AU - Herzog, Andrea
AU - Gerstenbauer, Gabi
AU - Konetschny, Christian
AU - Zimmermann, Klaus
AU - Scharrer, Inge
AU - Peyvandi, Flora
AU - Galbusera, Miriam
AU - Remuzzi, Giuseppe
AU - Böhm, Martina
AU - Plaimauer, Barbara
AU - Lämmle, Bernhard
AU - Scheiflinger, Friedrich
PY - 2005/8/15
Y1 - 2005/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=23744486523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23744486523&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-11-4490
DO - 10.1182/blood-2004-11-4490
M3 - Article
C2 - 15890682
AN - SCOPUS:23744486523
VL - 106
SP - 1262
EP - 1267
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -