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A Cellular Viewpoint of Anti-FVIII Immune Response in Hemophilia A

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Abstract

A large proportion of hemophilia A patients who receive replacement therapy, develop an immune response toward the infused factor VIII (FVIII). In this review, we discuss recent progress in several aspects of the anti-FVIII immune response, focusing on the sites of FVIII endocytosis (marginal zone of the spleen and bleeding site), the type of antigen-presenting cells (dendritic cells, macrophages and B cells) and endocytic receptors, implicated in FVIII presentation to T cells during primary and secondary immune response. Although it is becoming increasingly clear that regulatory T cells are involved in FVIII tolerance in healthy subjects and potentially in patients without inhibitors, we would like to demonstrate that little is known about the different T cells subsets and the cytokines network, which are also crucial for the development of allo- and autoimmune diseases. As more information on these issues becomes available, a better understanding of the role of each immune cells compartment in promoting FVIII tolerance or inhibitors development might lead to new strategies to promote FVIII tolerance in hemophilia A patients.

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Acknowledgment

Our work is supported by research grants from Institut National de la Santé et de la Recherche Médicale, by Centre National de la Recherche Scientifique, by Université Pierre et Marie Curie, by Agence Nationale de la Recherche (ANR-05-MRAR-030, ANR-07-JCJC-0100-01, ANR-07-RIB-002-02, ANR-07-MRAR-028-01), by Grifols (Barcelona, Spain), CSL-Behring (Marburg, Germany) and LFB (Les Ulis, France). SD is the recipient of a fellowship from Fondation pour la Recherche Médicale.

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  1. INSERM UMRS 872, Equipe 16, Centre de Recherche des Cordeliers, 15, rue de l’Ecole de Médecine, 75006, Paris, France

    Sebastien André, Yann Meslier, Jordan D. Dimitrov, Yohann Repessé, Srinivas V. Kaveri, Sebastien Lacroix-Desmazes & Suryasarathi Dasgupta

  2. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, 15 rue de l’Ecole de Médecine, Paris, F-75006, France

    Sebastien André, Yann Meslier, Jordan D. Dimitrov, Yohann Repessé, Srinivas V. Kaveri, Sebastien Lacroix-Desmazes & Suryasarathi Dasgupta

  3. Université Paris Descartes, UMR S 872, Paris, F-75006, France

    Sebastien André, Yann Meslier, Jordan D. Dimitrov, Yohann Repessé, Srinivas V. Kaveri, Sebastien Lacroix-Desmazes & Suryasarathi Dasgupta

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  1. Sebastien André
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  2. Yann Meslier
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  3. Jordan D. Dimitrov
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Correspondence to Sebastien Lacroix-Desmazes or Suryasarathi Dasgupta.

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André, S., Meslier, Y., Dimitrov, J.D. et al. A Cellular Viewpoint of Anti-FVIII Immune Response in Hemophilia A. Clinic Rev Allerg Immunol 37, 105–113 (2009). https://doi.org/10.1007/s12016-009-8117-2

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