Autoantibody Selectively Inhibits Binding of von Willebrand Factor to Glycoprotein Ib. Recognition Site Is Located in the A1 Loop of von Willebrand Factor

Hiroshi Mohri; Etsuko Yamazaki; Zekou Suzuki; Toshikuni Takano; Shumpei Yokota; Takao Okubo

doi:10.1055/s-0038-1656047

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(04): 760-766
DOI: 10.1055/s-0038-1656047

von Willebrand Factor

Schattauer GmbH Stuttgart

Autoantibody Selectively Inhibits Binding of von Willebrand Factor to Glycoprotein Ib. Recognition Site Is Located in the A1 Loop of von Willebrand Factor

Authors

Hiroshi Mohri

¹The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama
Etsuko Yamazaki

¹The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama
Zekou Suzuki

³The Department of Clinical Laboratory, Iwate Medical School, Morioka
Toshikuni Takano

⁴The Department of Pediatrics, Iwate Medical School, Morioka, Japan
Shumpei Yokota

²The Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan
Takao Okubo

¹The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama

Abstract

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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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References

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