Epitope specificity and inactivation mechanisms of factor VIII inhibitor antibodies.

Abstract:

:The domain specificity of anti-factor VIII (FVIII) inhibitor antibodies was determined in assays using FVIII domains generated by thrombin cleavage or expressed as recombinant polypeptides to neutralise the inhibitor. The results revealed the existence of three major types of inhibitors, and various combinations of these antibodies were found in haemophilic and autoantibody patients. Anti-A2 domain inhibitors prevent normal function of the FVIII/factor IXa (FIXa)/phospholipid complex in an unknown manner. Binding of FVIII to phospholipid and to von Willebrand factor is blocked by anti-C2 domain antibodies, and the binding of FVIII to FIXa is prevented by anti-A3 domain antibodies. A rare type of inhibitor prevents release of activated FVIII from von Willebrand factor (vWf), and another probably interferes with FVIII binding to factor X (FX) because it shares the epitope of a monoclonal antibody with this property.

journal_name

Vox Sang

journal_title

Vox sanguinis

authors

Scandella D

doi

10.1159/000056708

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

17-20

eissn

0042-9007

issn

1423-0410

pii

56708

journal_volume

77 Suppl 1

pub_type

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    pub_type: 杂志文章,评审

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    doi:10.1111/j.1423-0410.2008.01037.x

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  • A simple protocol for the screening and preliminary identification of antibodies to human IgA using unpurified proteins in the passive haemagglutination test.

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    authors: Bakkour S,Chafets DM,Wen L,van der Meer PF,Mundt JM,Marschner S,Goodrich RP,Busch MP,Lee TH

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