title: Acquired thrombotic thrombocytopenic purpura. Development of an autoimmune response.
abstract: 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.
authors: University Clinic of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital and the University of Bern, 3010 Bern, Switzerland. monica.schaller@insel.ch.
authors: M
authors: M
authors: Schaller
authors: J-D
authors: JD
authors: Studt
authors: J
authors: J
authors: Voorberg
authors: J A
authors: JA
authors: Kremer Hovinga
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014841:von Willebrand Factor / Q000276:immunology*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human