Inhibitors - cellular aspects and novel approaches for tolerance.
The immune response against therapeutic clotting factors VIII and IX (FVIII and FIX) is a major adverse event that can effectively thwart their effectiveness in correcting bleeding disorders. Thus, a significant number of haemophilia patients form antibodies, called inhibitors, which neutralize the procoagulant functions of therapeutic cofactors FVIII (haemophilia A) or FIX (haemophilia B). Understanding the cellular and molecular aspects of inhibitor formation is critical to designing tolerogenic therapies for clinical use. This review will focus on the basis of the immune response to FVIII, in particular, and will discuss emerging efforts to not only reduce immunogenicity but also to prevent and/or reverse inhibitor formation.
Department of Medicine, Uniformed Services, University for the Health Sciences, Bethesda, MD, USA.
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Scott
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D005164:Factor IX / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D002836:Hemophilia B / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007167:Immunotherapy; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D007074:Immunoglobulin G; D007518:Isoantibodies; D005169:Factor VIII; D005164:Factor IX
factor VIII; gene therapy; haemophilia; immunoglobulin fusions; regulatory T cells