Blood, 1973, Vol. 42, No. 3, pp. 437-444.
© 1973 American Society of Hematology, Inc.
Antibodies to Factor VIII. I. Variations in
Stability of Antigen-Antibody
Complexes in Hemophilia A
J.-P. Allain 1 and
D. Frommel 1
1 Centre pour Enfants Hémophiles, Croix-Rouge Française, La Queue lez Yvelines, and
the Centre National de Transfusion Sanguine, Paris, France.
Human factor VIII-anti-factor VIII complexes were formed in vitro in slight antigen excess, using plasma of hemophiliacs
who were found to have antibodies neutralizing AHF activity. These complexes,
stable at +37°C and pH 7.4, were submitted to classical procedures known to
favor dissociation of antibody from antigen.
The methods used to obtain dissociation,
incubations at +56°C and at pH 4.2, inactivated both unbound factor VIII and that
released as a consequence of dissociation.
The extent of dissociation was measured
by the recovery of anti-factor VIII activity.
Increasing resistance of complexes towards dissociation was observed in the
plasma of the patients whose titer of inhibitor was increasing after recent transfusions. These observations suggested the
emergence, as a direct consequence of renewed antigenic stimulation, of a population of different antibodies characterized
by higher combining strength.
Submitted on November 27, 1972
Revised on March 5, 1973
Accepted on March 6, 1973