12. Immunology of Inhibitor Development

  1. Emérito-Carlos Rodríguez-Merchán MD, PHD2,3 and
  2. Leonard A. Valentino MD4
  1. Birgit M. Reipert PhD,
  2. Christoph J. Hofbauer Dipl.-Ing. (FH),
  3. Katharina N. Steinitz Mag Rer Nat,
  4. Hans-Peter Schwarz MD, PhD and
  5. Frank M. Horling PhD

Published Online: 12 MAY 2011

DOI: 10.1002/9781119979401.ch12

Current and Future Issues in Hemophilia Care

Current and Future Issues in Hemophilia Care

How to Cite

Reipert, B. M., Hofbauer, C. J., Steinitz, K. N., Schwarz, H.-P. and Horling, F. M. (2011) Immunology of Inhibitor Development, in Current and Future Issues in Hemophilia Care (eds E.-C. Rodríguez-Merchán and L. A. Valentino), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781119979401.ch12

Editor Information

  1. 2

    Department of Orthopedic Surgery and Hemophilia Unit, La Paz University Hospital, Spain

  2. 3

    School of Medicine, Autonomous University, Madrid, Spain

  3. 4

    Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA

Author Information

  1. Baxter Innovation GmbH, Vienna, Austria

Publication History

  1. Published Online: 12 MAY 2011
  2. Published Print: 13 MAY 2011

ISBN Information

Print ISBN: 9780470670576

Online ISBN: 9781119979401



  • hemophilia A;
  • FVIII inhibitors;
  • T-cell dependent antibody response;
  • T-cell independent antibody response;
  • immune regulation


This review summarizes the current knowledge of the immunological mechanisms that are responsible for the development of antibodies against factor VIII in patients with hemophilia A who receive replacement therapy.

The generation of high affinity antibodies against protein antigens such as FVIII is believed to require cognate interactions between B cells and CD4+ helper T cells. These interactions are thought to initiate somatic hypermutations of immunoglobulin genes for affinity maturation of antibodies and to facilitate class-switch recombination for generation of IgG, IgA or IgE antibodies. However, based on current knowledge, it cannot be excluded that antibody responses against proteins such as FVIII could also occur in a T-cell independent way. Such antibodies should be of low affinity due to the lack of affinity maturation.