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DOI: 10.1055/s-0038-1656047
Autoantibody Selectively Inhibits Binding of von Willebrand Factor to Glycoprotein Ib. Recognition Site Is Located in the A1 Loop of von Willebrand Factor
Publication History
Received 25 July 1996
Accepted after resubmission 12 December 1996
Publication Date:
11 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199704/lookinside/thumbnails/10-1055-s-0038-1656047-1.jpg)
Summary
A 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first autoantibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.
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