title: Targeting FcγRs to treat antibody-dependent autoimmunity.
abstract: Self-reactive antibodies represent a significant force in autoimmune disease induction. In antibody-dependent autoimmune syndromes such as immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), myasthenia gravis and rheumatoid arthritis (RA), autoantibodies exert their inflammatory effect through FcγRs, a well-established class of cell surface receptors that interact with the Fc domain of IgG. Down-regulating FcγR functionality presents an attractive strategy to treat antibody-dependent autoimmune diseases. Various approaches, including nonspecific blocking of the IgG binding site as well as specific targeting using antagonistic monoclonal antibodies, have been explored to modulate the interaction between the Fc portion of IgG and FcγRs. The exquisite specificity and favorable pharmacokinetics of IgG make monoclonal antibodies a preferred choice. Indeed, the first antagonistic monoclonal antibody against the human FcγRIIIA had shown efficacy in refractory ITP patients; however, the practicality of using anti-FcγRIII antibody as a therapeutic was hindered by its associated adverse events, a phenomenon recapitulated in animal models. In this review, we discuss the role of FcγRs in autoimmune diseases, and focus on a novel monovalent approach to target FcγRs to resolve antibody-mediated autoimmunity.
authors: Canadian Blood Services, Ottawa, Ontario, Canada K1G 4J5; Department of Laboratory Medicine, The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada, M5B 1W8.
authors: Xiaojie
authors: X
authors: Yu
authors: Canadian Blood Services, Ottawa, Ontario, Canada K1G 4J5; Department of Laboratory Medicine, The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada, M5B 1W8; Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada, M5S 1A8. Electronic address: LAZARUSA@smh.ca.
authors: Alan H
authors: AH
authors: Lazarus
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D017452:Receptors, IgG / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D017452:Receptors, IgG
keywords: Albumin fusion protein; Autoimmunity; Fc receptors; Monoclonal antibody; Monovalent targeting