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Maternally transferred anti‐factor VIII IgG reduce the anti‐factor VIII humoral immune response in factor VIII‐deficient mice
Author(s) -
Meslier Yann,
André Sébastien,
Teyssandier Maud,
Kaveri Srinivas V.,
LacroixDesmazes Sébastien
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03327.x
Subject(s) - immunology , immune system , offspring , haemophilia a , antibody , haemophilia , immunoglobulin g , lymphocyte , biology , immune tolerance , medicine , pregnancy , genetics
Summary Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or used in prophylaxis induces inhibitory anti‐FVIII immunoglobulin G (IgG) in some patients with haemophilia A. Therapeutic strategies to prevent the onset of the deleterious anti‐FVIII immune response are still lacking. Maternal IgG is transferred to the offspring during fetal and neonatal life. While protecting the offspring from bacterial and viral infections, maternal IgG may alter the repertoires of T and B lymphocytes, and may impair vaccination in early infancy. Using haemophilic mice, we demonstrate that the transfer of maternal anti‐FVIII IgG modulates the onset of anti‐FVIII inhibitory IgG in early adulthood. The protective effect is reproduced upon reconstitution of naive mice with anti‐FVIII IgG, suggesting that the reduced ability to mount an anti‐FVIII immune response is the result of an interference between circulating anti‐FVIII IgG and the administered FVIII rather than to a profound remodelling of lymphocyte repertoires occurring during the ontogeny of the immune system.