Tumor necrosis factor receptor p55 and p75 deficiency protects mice from developing experimental autoimmune myasthenia gravis.
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.
Goluszko
Elzbieta
E
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, 3.142 MRB, Galveston, TX 77555-1070, USA.
Deng
Caishu
C
Poussin
Mathilde A
MA
Christadoss
Premkumar
P
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
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