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Thromb Haemost 1999; 81(05): 793-798
DOI: 10.1055/s-0037-1614572
Rapid Communication
Schattauer GmbH

Identification of the Binding Site for an Alloantibody to von Willebrand Factor which Inhibits Binding to Glycoprotein Ib within the Amino-terminal Region Flanking the A1 Domain

Masaru Shibata
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
,
Midori Shima
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
,
Yoshihiro Fujimura
2   Blood Transfusion, Nara Medical University, Kashihara Japan, the Kagoshima City Hospital, Kagoshima, Japan
,
Yukihiro Takahashi
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
,
Hiroaki Nakai
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
,
Yoshihiko Sakurai
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
,
Masayo Asatani
3   Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan; and the, Cardiff, UK
,
Akihiko Nomura
3   Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan; and the, Cardiff, UK
,
Hiromichi Take
3   Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan; and the, Cardiff, UK
,
John C. Giddings
4   Department of Haematology, University of Wales College of Medicine, Cardiff, UK
,
Akira Yoshioka
1   From the Departments of Pediatrics and, Nara Medical University, Kashihara Japan
› Author Affiliations
Further Information

Publication History

Received 09 June 1998

Accepted after resubmission 27 January 1999

Publication Date:
09 December 2017 (online)

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Summary

An alloantibody to von Willebrand factor (vWF) which developed in a Japanese boy with type 3 von Willebrand disease has been characterized. The antibody was non-precipitating IgG and the main subclasses were IgG2 and IgG4. The antibody inhibited completely ristocetin-induced platelet aggregation (RIPA) and high shear stress-induced platelet aggregation (SIPA). Its predominant inhibitory role was focused, therefore, on the interaction between vWF and platelet gycoprotein Ib. The antibody reacted with a 52/48 kDa tryptic fragment of vWF (residues 449-728). No reaction was seen, however, with either a 39/34 kDa dispase fragment (480-718) or a recombinant vWF fragment (residues 465-728). These findings suggested that the essential epitope resided in the amino-terminal flanking region of the A1 domain. We synthesized overlapping peptides corresponding to the region containing D3/A1 boundary. A peptide, residues 458-472, bound to the antibody and dose-dependently blocked the antibody binding to the 52/48 kDa fragment. The same peptide neutralized the inhibitory effect of the alloanti-body on SIPA. The data are consistent with the presence of an epitope within residues 458-472 which reacted with the 52/48 kDa fragment.

Furthermore, the specific component of the antibody, directed against residues 458-472, blocked vWF binding to GPIb in absence of exogenous agonist. Our results suggest that the region flanking the A1 domain plays an important role in regulating vWF binding to GPIb.

 

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