Correlation between factor VIII genotype and inhibitor development in hemophilia A

被引:43
作者
Fakharzadeh, SS
Kazazian, HH
机构
[1] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
关键词
hemophilia A; factor VIII gene; factor VIII mutation; inhibitor;
D O I
10.1055/s-2000-9819
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The development of neutralizing antibodies, or inhibitors, against infused factor VIII represents a significant complication of treatment for hemophilia A. Although it is likely that both genetic and environmental factors influence whether patients form inhibitors, correlations between types of factor VIII mutations and inhibitor development are becoming apparent, Approximately 20% of all patients with severe hemophilia A generate inhibitors. Of these inhibitor patients, 90% have inversions, large deletions or nonsense mutations of the factor VIII gene that would be predicted to eliminate production of factor VIII antigen. In contrast to patients with severe disease, inhibitor formation in patients with mild/moderate hemophilia A is rare. Inhibitor patients with mild/moderate disease typically have missense mutations that may cause local conformational changes within immunogenic domains of factor VIII and lead to production of dysfunctional antigen. Taken together, hemophilia A patients are predisposed to inhibitor development with mutations causing infused factor VIII to be perceived as either 1) a completely novel antigen or 2) an immunologically altered antigen.
引用
收藏
页码:167 / 171
页数:5
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