REDUCED ANTIGENIC REACTIVITY IN VARIANTS OF VONWILLEBRANDS DISEASE

Factor VIII related antigen (VIIIR:AG) was measured in 49 cases of von Willebrand’s disease (vWd) by an immunoradiometric assay (coated tube system), using purified IgG prepared from antisera raised in both a rabbit and a goat. The control dose-response curve showed a linear relationship between bound radioactivity and log plasma dilutions between 1:25,000 and 1:400. At higher concentrations of plasma (i. e. lower dilutions), the percentage of bound radioactivity reached a plateau. In severe cases of vWd, no measurable VIIIR:AG (<1.10-4 u/ml) was detected. Most of the other patients had a normal response pattern with reduced levels of antigen. This contrasted with 13 patients who showed an abnormal dose-response curve. In all 13 cases, the maximal percentage of bound radioactivity (plateau) was lower than in the normal. These patients had a 20–30% absolute reduction of antibody binding capacity. This phenomenon was obtained with both rabbit and goat antibody. In addition, 4 of these patients (from 2 families) showed a lack of parallelism to the normal in the linear portion of their dose-response curve. This lack of parallelism only occurred with the rabbit and not with the goat antibody. All of these 13 patients fulfilled the criteria for “variants” of vWd, i. e. abnormal electrophoretic mobility and a disproportionately reduced Willebrand Factor activity in comparison to VIIIR:AG. These abnormalities of the immunoradiometric response are further evidence that an abnormal protein with reduced antigenic reactivity is present in “variants” of von Willebrand’s disease.