title: Antidrug Antibodies: B Cell Immunity Against Therapy.
abstract: Chronic inflammatory diseases are now treated with a range of different biopharmaceuticals, often requiring lifelong parenteral administrations. This exposure to drugs is unnatural and can trigger the immune system and result in the formation of antidrug antibodies. Drug-specific antibodies will, if of sufficiently high titre and affinity, block the intended effect of the drug, increase its clearance and make continued treatment worthless. We expect the immune system to react towards therapies against which tolerance has never been established, which is the case for factor VIII treatment in patients with haemophilia A. However, even biopharmaceutical molecules that we should be tolerant against can elicit antidrug antibodies, for instance in treatment of multiple sclerosis patients with recombinant human interferon-beta. Possible immunological mechanisms behind the breaking of tolerance against drugs, the impact this has on continuous treatment success, clinical practice and drug development, will be discussed in this review.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Clinical Neuroimmunology, Center for Molecular Medicine (CMM), Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Fogdell-Hahn
mesh_terms: D000906:Antibodies / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy; D000069442:Natalizumab; D004364:Pharmaceutical Preparations; D017211:Treatment Failure
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000069442:Natalizumab; D004364:Pharmaceutical Preparations; C427184:recombinant factor VIII SQ; D016899:Interferon-beta; D005169:Factor VIII