HETEROGENEITY OF AUTOANTIBODIES TO FACTOR-VIII - DIFFERENCES IN SPECIFICITY FOR APPARENTLY DISTINCT ANTIGENIC DETERMINANTS OF FACTOR-VIII COAGULANT PROTEIN

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 62  (1) , 133-140
Abstract
The interference of antibodies to factor VIII coagulant protein (VIII:C) of 9 nonhemophilic patients with the binding to factor VIII coagulant antigen (VIII:CAg) of a reference hemophilic 125I-Fab'' reagent, used in a liquid phase VIII:CAg assay, was studied. The binding competition was estimated from immunoradiometric assay dose-response slope of VIII:CAg present in patient plasma, interference of antibodies with the 125I-Fab'' bnding to VIII:CAg in normal plasma, and the displacement of antibody from the complexes with VIII:CAg by the 125I Fab''. Antibody populations from 3 patients were studied in detail; in the VIII:CAg assay, 2 of them interfered with the 125I-Fab'' binding, and 1 did not (patient 1). The formation of stable complexes between antibodies of each patient and VIII:CAg was demonstrated by protein A-Sepharose adsorption. The 25I-Fab'' binding to VIII:CAg-anti-VIII:CAg IgG complexes indicated that patient 1 antibodies and the 125I-Fab'' recognized different antigenic determinants, whereas the other 2 patient antibodies and 125I-Fab'' recognized closely related or identical VIII:CAg determinants. The results demonstrate an apparently selective recognition of at least 2 distinct VIII:CAg determinants by naturally occurring antibodies, suggesting a possibility of a wider use of these antibodies in studies of the structure and function of factor VIII.