Evidence for a role of anti-ADAMTS13 autoantibodies despite normal ADAMTS13 activity in recurrent thrombotic thrombocytopenic purpura
- 11 October 2011
- journal article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 97 (2), 297-303
- https://doi.org/10.3324/haematol.2011.051433
Abstract
Severe ADAMTS13 deficiency is a critical component of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura but is found only in about 60% of patients clinically diagnosed with this disease. Over a period of 8 years and six episodes of thrombotic thrombocytopenic purpura we studied the evolution of the anti-ADAMTS13 antibody response in a patient using different ADAMTS13 assays and epitope mapping. Anti-ADAMTS13 autoantibodies were found in all episodes but were inhibitory only in the last two episodes. In a flow-based assay, normal ADAMTS13 activity was found only during the first disease episode, while ADAMTS13 activity was normal using a static assay in episodes 1 and 3, and severely deficient in the last two episodes. Fluorescence evolution in a modified fluorescence resonance energy transfer assay using a von Willebrand factor A2 domain peptide substrate was linear in episodes 1, 5 and 6, but increased exponentially in episodes 3 and 4. Despite the variable functional characteristics of the anti-ADAMTS13 autoantibodies, their principal epitope was the ADAMTS13 spacer domain in all episodes. The patient is unique as he displayed features of maturation or shaping of the anti-ADAMTS13 autoantibody response during the course of multiple episodes of thrombotic thrombocytopenic purpura. Anti-ADAMTS13 autoantibodies may be important in vivo despite normal ADAMTS13 activity in routine assays. Consequently, treatment decisions should not be based solely on activity assay results.Keywords
This publication has 27 references indexed in Scilit:
- Systemic infections mimicking thrombotic thrombocytopenic purpuraAmerican Journal of Hematology, 2011
- The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpuraThrombosis and Haemostasis, 2005
- Measurement of von Willebrand factor cleaving protease (ADAMTS‐13): results of an international collaborative study involving 11 methods testing the same set of coded plasmasJournal of Thrombosis and Haemostasis, 2004
- Measurement of von Willebrand factor-cleaving protease (ADAMTS-13) activity in plasma: a multicenter comparison of different assay methodsJournal of Thrombosis and Haemostasis, 2003
- HIV and autoimmunityAutoimmunity Reviews, 2002
- ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditionsBlood, 2002
- Thrombotic MicroangiopathiesThe New England Journal of Medicine, 2002
- von Willebrand Factor–Cleaving Protease in Thrombotic Thrombocytopenic Purpura and the Hemolytic–Uremic SyndromeThe New England Journal of Medicine, 1998
- Clinical implications of autoantibodies in HIV infectionAIDS, 1997
- Abnormalities of B-Cell Activation and Immunoregulation in Patients with the Acquired Immunodeficiency SyndromeThe New England Journal of Medicine, 1983