title: Tumor necrosis factor receptor p55 and p75 deficiency protects mice from developing experimental autoimmune myasthenia gravis.
abstract: The precise pathogenic role of proinflammatory cytokines belonging to the tumor necrosis factor (TNF) family has not been investigated yet in antibody-mediated myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG). In this study we report that TNF receptor p55(-/-) p75(-/-) mice were resistant to the development of clinical EAMG induced by acetylcholine receptor (AChR) immunizations. The resistance was associated with reduced serum levels of IgG, IgG(1), IgG(2a), and IgG(2b) anti-AChR antibody isotypes. However, IgM anti-AChR antibodies were not reduced, suggesting defective anti-AChR IgG class switching in TNF receptor p55(-/-) p75(-/-) mice. We thus demonstrate the genetic evidence for the role of TNF receptor p55 and p75 in EAMG pathogenesis, and their requirement for the generation of anti-AChR IgG antibodies.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, 3.142 MRB, Galveston, TX 77555-1070, USA.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Goluszko
authors.forename: Caishu
authors.initials: C
authors.lastname: Deng
authors.forename: Mathilde A
authors.initials: MA
authors.lastname: Poussin
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008233:Lymphotoxin-alpha; D011950:Receptors, Cholinergic; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha