High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors
High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors
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DOI：
10.1182/blood-2005-03-1182
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发表时间：
2005-11-15
期刊：
影响因子：
20.3
通讯作者：
Reipert, BM
中科院分区：
文献类型：
--
作者：
Hausl, C;Ahmad, RU;Reipert, BM
Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is caused by mutations in the factor VIII (FVIII) gene (symbol F8). About 25% of patients who receive replacement therapy develop neutralizing antibodies that inhibit the function of substituted FVIII. Long-term application of high doses of FVIII has evolved as an effective therapy to eradicate the antibodies and to induce long-lasting immune tolerance. Little is known, however, about the immunologic mechanisms that cause the down-modulation of anti-FVIII antibodies by high doses of FVIII. We report that high doses of FVIII inhibit the restimulation of FVIII-specific memory B cells and their differentiation into anti body-secreting plasma cells in vitro and in vivo in a murine model of hemophilia A. The inhibition of memory B-cell responses is irreversible and not mediated by FVIII-specific T cells. Further-more, it seems to involve the activation of caspases. We conclude that the inhibition of FVIII-specific memory B cells might be an early event in the down-modulation of anti-FVIII antibodies in patients with hemophilia A who receive high doses of FVIII.
