title: Acquired TTP: ADAMTS13 meets the immune system.
abstract: The majority of the patients affected by acquired thrombotic thrombocytopenic purpura (TTP) develop autoantibodies directed towards ADAMTS13 that interfere with its von Willebrand Factor (VWF) processing activity. B cell responses have been shown to primarily target the spacer domain of ADAMTS13 thereby prohibiting the binding of ADAMTS13 to the VWF A2 domain. In this review we summarize recent knowledge gained on the immune recognition and processing of ADAMTS13 by antigen-presenting cells (APCs). HLA-DRB1*11 has been identified as a risk factor for acquired TTP. Analysis of MHC class II/peptide complexes of ADAMTS13 pulsed dendritic cells have shown that the CUB2 domain derived peptide FINVAPHAR is preferentially presented on HLA-DRB1*11. Based on these findings we propose a model for the initiation of the autoimmune reactivity against ADAMTS13 in previously healthy individuals. We hypothesize that mimicry between a pathogen-derived peptide and the CUB2 derived FINVAPHAR-peptide might contribute to the onset of acquired TTP.
authors.affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: Fabian C
authors.initials: FC
authors.lastname: Verbij
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands. Electronic address: j.voorberg@sanquin.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Voorberg
authors.affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sorvillo
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000938:Antigen-Presenting Cells / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Antibodies; Glycosylation; Molecular mimicry; Review; TTP; Thrombotic thrombocytopenic purpura