title: Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral immune response in factor VIII-deficient mice.
abstract: 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.
authors.affiliation: INSERM U872, Centre de recherche des Cordeliers, Paris, France. yann.meslier@crc.jussieu.fr
authors.forename: Yann
authors.initials: Y
authors.lastname: Meslier
authors.forename: Sébastien
authors.initials: S
authors.lastname: André
authors.forename: Maud
authors.initials: M
authors.lastname: Teyssandier
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000276:immunology*; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D007074:Immunoglobulin G; C078147:F8 protein, human; D005169:Factor VIII