In hemophilia A and autoantibody inhibitor patients: The factor VIII A2 domain and light chain are most immunogenic

被引：40

作者：

Scandella, DH ^{[1
]}

Nakai, H ^{[1
]}

Felch, M ^{[1
]}

Mondorf, W ^{[1
]}

Scharrer, I ^{[1
]}

Hoyer, LW ^{[1
]}

Saenko, EL ^{[1
]}

机构：

[1] Amer Red Cross, Dept Immunol, Rockville, MD 20855 USA

来源：

THROMBOSIS RESEARCH | 2001年 / 101卷 / 05期

关键词：

factor VIII; inhibitor antibody; autoantibody; factor VIII domain; immunogenicity;

D O I：

10.1016/S0049-3848(00)00418-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Factor VIII (fVIII) is a protein cofactor essential for blood coagulation, and it binds in the factor Xase complex to factors IXa, X, and phospholipid. In about 30% of severe hemophilia A patients, treatment with fVIII leads to production of anti-fVIII antibodies. Anti-fVIII autoantibodies also rarely appear in normal individuals. Those antibodies that inactivate fVIII (inhibitors) prevent optimal fVIII, therapy. Inhibitor epitopes were previously localized to the fVIII A2, A3, and C2 domains and to an acidic amino acid region between Al and A2. Such anti-fVIII antibodies interfere with fVIII binding to components of the factor Xase complex and prevent blood coagulation. When total anti-fVIII titers were determined for each fVIII domain in 43 inhibitor plasmas by immunoprecipitation (IP) and inhibitor neutralization assays, the anti-light chain (LCh) antibody titer was highest, anti-A2 was intermediate, and anti-Al and anti-B were low. The relative immunogenicity of the fVIII domains in hemophilic and autoantibody inhibiter patients was similar. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：377 / 385

页数：9

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