Abnormal antigenic reactivity of factor VIII/von Willebrand factor subunit in variants of von Willebrand's disease.
Antibodies specific for either the subunit (MW 2.4 X 10(5)) or conformational antigenic determinants of F.VIII/vWF were prepared in order to investigate further the abnormal antigenic reactivity in variants of vWD. Goat anti-human F.VIII/vWF Fab fragments were immunoadsorbed with F.VIII/vWF subunits bound to activated thiol-Sepharose, and the "anti-subunit" antibody was eluted at pH 2.4. Antibodies that did not bind to the beads were designated as "anti-conformation" antibody. The anti-subunit specifically reacted by IRMA with the F.VIII/vWF subunits and with all subunit-containing multimers (MW 4.8 X 10(5) to greater than 15 X 10(6)). The anti-conformation antibody failed to react with F.VIII/vWF subunits but reacted with native (MW 1 to greater than 15 X 10(6)) or partially reduced (MW 4.8 X 10(5)) F.VIII/vWF. It was thus specific for antigenic sites resulting from the association of subunits in dimers or multimers of F.VIII/vWF. In eight patients with a variant of vWD (type IIA), an abnormal antigenic reactivity in plasma, characterized by a dose-response curve not parallel to that of control, was consistently observed by IRMA using the anti-subunit antibody. Six showed a normal dose-response curve with the anti-conformation antibody, and two unique patients also demonstrated an abnormal (nonparallel) response. This study (1) allows the distinction between subunit and conformational antigenic sites on F.VIII/vWF, (2) demonstrates that the decreased antigenicity in type IIA vWD is associated in all cases with an abnormality of F.VIII/vWF subunits and in some patients with an additional defect of polymerization, and (3) further emphasizes the heterogeneity of variants of vWD.
D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000276:immunology*; D004587:Electrophoresis, Agar Gel; D000939:Epitopes; D005169:Factor VIII / Q000276:immunology*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D011863:Radioimmunoassay; D014842:von Willebrand Diseases / Q000276:immunology*; D014841:von Willebrand Factor / Q000276:immunology*
D001779:Blood Coagulation Factors; D000939:Epitopes; D014841:von Willebrand Factor; D005169:Factor VIII