title: Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris.
abstract: Pemphigus vulgaris is a life-threatening autoimmune blistering disease caused by anti-desmoglein IgG autoantibodies that finally lead to acantholysis presenting clinically as progressive blistering. Whilst the production of pathogenic antibodies is key to the development of pemphigus vulgaris, many immunological steps are required prior to autoantibody induction. We review advances in the understanding of these immunologic processes with a focus on human leucocyte antigen polymorphisms and antigen recognition, epitope spreading, central and peripheral tolerance, T helper differentiation, induction of pro- and anti-inflammatory cytokines and T-cell regulation of B cells. Targeting autoaggressive T cells as regulators and stimulators of B-cell antibody production should allow for more specific therapeutic immune interventions, avoiding the global immunosuppression seen with many commonly used immunosuppressants in pemphigus vulgaris.
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Kyle T
authors.initials: KT
authors.lastname: Amber
authors.forename: Patrick
authors.initials: P
authors.lastname: Staropoli
authors.forename: Michael I
authors.initials: MI
authors.lastname: Shiman
authors.forename: George W
authors.initials: GW
authors.lastname: Elgart
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
mesh_terms: D000051:Acantholysis / Q000276:immunology; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D051184:Desmoglein 3 / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D008822:Mice, Transgenic; D010392:Pemphigus / Q000188:drug therapy* / Q000276:immunology*; D011110:Polymorphism, Genetic; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D051184:Desmoglein 3; D000939:Epitopes; D006680:HLA Antigens; D007074:Immunoglobulin G; D000069283:Rituximab
keywords: B cell; HLA class II; T cell; autoantigen; desmoglein; pemphigus vulgaris; rituximab