Acquired thrombotic thrombocytopenic purpura. Development of an autoimmune response

• Published in: Hämostaseologie Vol. 33; no. 2; p. 121
• Main Authors: Schaller, M, Studt, J-D, Voorberg, J, Kremer Hovinga, J A
• Format: Journal Article
• Language: English
• Published: Germany 29.05.2013
• Subjects: ADAM Proteins - immunology; ADAMTS13 Protein; Autoimmunity - immunology; B-Lymphocytes - immunology; Humans; Models, Immunological; Purpura, Thrombotic Thrombocytopenic - immunology; Purpura, Thrombotic Thrombocytopenic - pathology; T-Lymphocytes - immunology; von Willebrand Factor - immunology
• ISSN: 0720-9355
• DOI: 10.5482/HAMO-12-12-0023

The von Willebrand factor (VWF)-cleaving metalloprotease, ADAMTS13 (adisintegrin and metalloprotease with thrombospondin type 1 motifs-13) is the only known target of the dysregulated immune response in acquired TTP. Autoantibodies to ADAMTS13 either neutralize its activity or accelerate its clearance, thereby causing a severe deficiency of ADAMTS13 in plasma. As a consequence, size regulation of VWF is impaired and the persistence of ultra-large VWF (ULVWF) multimers facilitates microvascular platelet aggregation causing microangiopathic haemolytic anaemia and ischaemic organ damage. Autoimmune TTP although a rare disease with an annual incidence of 1.72 cases has a mortality rate of 20% even with adequate therapy. We describe the mechanisms involved in ADAMTS13 autoimmunity with a focus on the role of B- and T-cells in the pathogenesis of this disorder. We discuss the potential translation of recent experimental findings into future therapeutic concepts for the treatment of acquired TTP.