IDENTIFICATION OF A FVIII EPITOPE RECOGNIZED BY A HUMAN HEMOPHILIC INHIBITOR
- 1 February 1989
- journal article
- research article
- Vol. 73 (2) , 497-499
Abstract
Hemophilia A, one of the most common of the inherited bleeding disorders, results from a deficiency or abnormality of factor VIII (F.VIII). In .apprx.15% of persons with hemophilia, treatment with exogenous F.VIII is complicated by the development of anti-F.VIII antibodies which block F.VIII coagulent activity. These antibodies have been termed inhibitors. To localized epitopes recognized by inhibitors, we used a .lambda.gt11 library which expresses small random fragments of F.VIII as fusion proteins. One epitope has been mapped to the 25-amino acid sequence lys-338 through asp-362 of F.VIII (E338-362). Immunoaffinity-purified antibodies that react with this epitope neutralize F.VIII:C activity. E338-362 is adjacent to an enzymatic cleavage site at arg-372 which is important in F.VIII activation. Hence, an antibody binding to E338-362 would probably block this cleavage and thereby block activation of F.VIII.This publication has 9 references indexed in Scilit:
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