title: Role of ADAMTS13 in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura.
abstract: The regulation of VWF multimer size is essential in preventing spontaneous microvascular platelet clumping, a central pathophysiologic finding in thrombotic thrombocytopenic purpura (TTP). In the majority of TTP patients, ADAMTS13, the principal regulator of VWF size, is severely deficient. Today, 2 forms of severe ADAMTS13 deficiency are recognized. The acquired form is caused by circulating autoantibodies inhibiting ADAMTS13 activity or increasing ADAMTS13 clearance. Pathogenic anti-ADAMTS13 Abs are mainly of the IgG class, predominantly of subclass IgG4, and inhibitory Abs recognize a defined epitope in the ADAMTS13 spacer domain. The reasons underlying the failure to maintain immunologic tolerance to ADAMTS13, however, are still poorly understood. Constitutional ADAMTS13 deficiency leading to hereditary TTP, also known as Upshaw-Schulman syndrome, is the result of homozygous or compound heterozygous ADAMTS13 gene mutations.
authors.affiliation: Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital and the University of Bern, Bern, Switzerland. johanna.kremer@insel.ch
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000502:physiology*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000941:Antigens / Q000378:metabolism; D001323:Autoantibodies / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006405:Hematology / Q000379:methods*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy*; D011994:Recombinant Proteins / Q000737:chemistry; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human