title: Novel animal models of acetylcholine receptor antibody-related myasthenia gravis.
abstract: Experimental autoimmune myasthenia gravis (EAMG) in mice has been used to unravel the pathogenic mechanisms and to be used as a preclinical model of myasthenia gravis (MG). Induction of predominantly ocular EAMG in HLA-DQ8 transgenic mice immunized with acetylcholine receptor (AChR) subunits demonstrated the importance of nonconformationally expressed AChR subunits in extraocular muscle involvement. Wild-type (WT) and CD4(+) T cell knockout (KO) C57BL/6 mice developed EAMG upon immunization with AChR in incomplete Freund's adjuvant plus lipopolysaccharide. AChR-specific IgG2(+) B cell frequencies, estimated by Alexa-conjugated AChR, and AChR-reactive IgG2b levels significantly correlated with the clinical grades of EAMG in WT mice. CD4(+) T cell-deficient EAMG mice exhibited AChR antibodies mainly of the IgG2b isotype, emphasizing T helper-independent B cell activation pathways in EAMG induction. These novel EAMG models have suggested that diverse immunopathological mechanisms might contribute to EAMG or MG pathogenesis.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, USA.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.forename: Windy
authors.initials: W
authors.lastname: Allman
authors.forename: Canan
authors.initials: C
authors.lastname: Ulusoy
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic