Semin Thromb Hemost 2000; Volume 26(Number 02): 173-178
DOI: 10.1055/s-2000-9820
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 760-0888

Potential for Prevention of Inhibitor Formation by Immune Tolerance

Joseph Kaplan, Carol Genyea, Elizabeth Secord
  • Department of Pediatrics, Wayne State University, Children's Hospital of Michigan, Detroit, Michigan
Further Information

Publication History

Publication Date:
31 December 2000 (online)

ABSTRACT

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.

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