Noncoagulation inhibitory factor VIII antibodies after induction of
tolerance to factor VIII in hemophilia A patients
IM Nilsson, E Berntorp, O Zettervall and B Dahlback
Department of Coagulation Disorders, University of Lund, Malmo General
Hospital, Sweden.
We recently described tolerance induction with factor VIII/IX,
cyclophosphamide, and high-dose intravenous IgG in hemophilia A or B
patients with coagulation inhibitory antibodies. Circulating noninhibitory
antibodies complexed with factor IX have been demonstrated in tolerant
hemophilia B patients. Similar findings are now described in six tolerant
hemophilia A patients. Complexes between factor VIII and the 'tolerant'
antibody were demonstrated by subjecting plasma to gel filtration
chromatography, void fractions containing factor VIII/vWF complexes being
collected and adsorbed to protein A. Using 125I-labeled F(ab')2 fragments
against IgG subclass and factor VIII antigen, complexes between an IgG4
antibody and factor VIII were found to adsorb to protein A. After infusion
of factor VIII to tolerant patients, all factor VIII circulated in complex
with IgG4 antibody. In three of the patients, the 'tolerant' antibodies
inhibited an ELISA specific for factor VIII light chain but, unlike the
pretolerant antibodies, did not bind radiolabeled factor VIII heavy chain.
Although after induction of tolerance the patients still have circulating
IgG4 antibodies against factor VIII, the antibodies differ in specificity,
lack coagulation inhibitory activity, and do not enhance the rate of
elimination of factor VIII.
Volume 75,
Issue 2,
pp. 378-383,
01/15/1990
Copyright © 1990 by The American Society of Hematology
