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Semin Thromb Hemost 2000; Volume 26(Number 02): 157-166
DOI: 10.1055/s-2000-9818
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 760-0888

Natural Antibodies to Factor VIII

Sébastien Lacroix-Desmazes, Alexandre Moreau, Anastas Pashov,  Sooryanarayana, Dorothea Stahl, Jean-Marie Saint-Remy, Srinivas V. Kaveri, Michel D. Kazatchkine
  • INSERM U430 and University Pierre et Marie Curie, Hôpital Broussais, Paris, France, and the CMVB, Katholieke Universiteit Leuven, Belgium
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Publikationsverlauf

Publikationsdatum:
31. Dezember 2000 (online)

    Lizenzen und Reprints

ABSTRACT

Anti-factor VIII antibodies represent a unique model to study the relationship between natural autoreactivity (natural antibodies to factor VIII of healthy individuals), disease-associated autoimmunity (``spontaneous'' factor VIII inhibitors of patients with anti-factor VIII autoimmune disease) and antigen-driven immune responses (immune inhibitors in multitransfused patients with hemophilia A) to a single human protein antigen. Although natural and disease-associated anti-factor VIII antibodies are not readily distinguished based on the comparison of their isotypic distribution and epitope mapping, available studies of cross-reacting idiotypes suggest that factor VIII inhibitors in patient's plasma encompass two populations of anti-factor VIII antibodies. Some antibodies result from the clonal expansion of B lymphocytes that exist before treatment with factor VIII and secrete anti-factor VIII antibodies with properties similar to those of natural anti-factor VIII antibodies present in healthy individuals; other inhibitors are produced by B cell clones that have undergone affinity maturation and hypermutation of the V regions of the antibodies they produce. The implications for the treatment of patients with anti-factor VIII inhibitors are discussed.

KEYWORD

Factor VIII - inhibitors - anti-idiotypes - natural antibodies - hemophilia A

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