title: A cellular viewpoint of anti-FVIII immune response in hemophilia A.
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.
authors.affiliation: INSERM UMRS 872, Equipe 16, Centre de Recherche des Cordeliers, 15, rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: André
authors.forename: Yann
authors.initials: Y
authors.lastname: Meslier
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.forename: Yohann
authors.initials: Y
authors.lastname: Repessé
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Suryasarathi
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D004705:Endocytosis; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D007074:Immunoglobulin G; D005169:Factor VIII