Factor VIII inhibitory antibodies occur following treatment in more than 30% of subjects
with severe factor VIII deficiency. Almost all inhibitor formation occurs in subjects
with little if any circulating factor VIII. In the absence of in utero exposure to
endogenous or maternal factor VIII, these subjects probably recognize factor VIII
as a non-self antigen; in other words, their immune systems fail to become tolerant
to factor VIII. This opens up the possibility of preventing inhibitor formation by
neonatal induction of tolerance to factor VIII. The various possible approaches include
prenatal or neonatal tolerance by the parenteral or oral administration of purified
factor VIII protein or factor VIII-encoding DNA. The results of preliminary experiments
in mice indicate that feeding newborns a series of low doses of factor VIII does not
suppress induction of anti-factor VIII antibody. Whether tolerance can be achieved
by feeding mice high doses of factor VIII or by intrauterine or neonatal administration
of factor protein or DNA remains to be determined.
Factor VIII inhibitors - immune tolerance - recombinant human factor VIII - oral tolerance
- DNA vaccines
