Factor VIII inhibitor in a patient with mild haemophilia A and an Asn618 →Ser mutation responsive to immune tolerance induction and cyclophosphamide

Autor:	Jan Voorberg, H. Marijke van den Berg, S. Wittebol, André J. Vlot, Paul F. W. Strengers, Ellen A. M. Turenhout, Eveline P. Mauser-Bunschoten
Rok vydání:	2002
Předmět:	biology business.industry Haemophilia A Hematology medicine.disease Immunoglobulin light chain Molecular biology Epitope Immune tolerance law.invention Epitope mapping law hemic and lymphatic diseases Immunology medicine biology.protein Recombinant DNA Antibody Binding site business
Zdroj:	British Journal of Haematology. 117:136-140
ISSN:	0007-1048
DOI:	10.1046/j.1365-2141.2002.03383.x
Popis:	We describe a patient with mild haemophilia A (original value of factor VIII activity 0.30 U/ml) who developed an inhibitor (36.1 Bethesda U/ml) which cross-reacted with his endogenous factor VIII. This caused a decline in basal factor VIII level ( Ser in the A2 domain of factor VIII. Immunoprecipitation analysis showed that the antibodies present in the patient's plasma reacted with metabolically labelled A2 domain and, to a lesser extent, with factor VIII light chain. Inhibitory antibodies were completely neutralized by recombinant A2 domain, whereas no neutralization was observed after the addition of factor VIII light chain (A3-C1-C2) and C2 domain. More detailed analysis showed that the majority of inhibitory antibodies were directed against residues Arg484-Ile508, a previously identified binding site for factor VIII inhibitors. Our findings suggest that immune tolerance therapy and cyclophosphamide were successful in eradicating inhibitory antibodies against a common epitope on factor VIII.
Databáze:	OpenAIRE
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