TY - JOUR
T1 - Tumor necrosis factor receptor p55 and p75 deficiency protects mice from developing experimental autoimmune myasthenia gravis
AU - Goluszko, Elzbieta
AU - Deng, Caishu
AU - Poussin, Mathilde A.
AU - Christadoss, Premkumar
N1 - Funding Information:
We thank Immunex, Seattle, WA, for providing us TNFR p55 −/− p75 −/− mice, and Mardelle Susman for editing the manuscript. This study was supported by Muscular Dystrophy Association and Association Francaise Contre les Myopathies. M. Poussin has a consecutive postdoctoral fellowship from the Association Francaise Contre les Myopathies, MG Foundation of America, and James W. McLaughlin Foundation. C. Deng was a James W. McLaughlin Foundation Postdoctoral Fellow.
PY - 2002
Y1 - 2002
N2 - 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, IgG1, IgG2a, and IgG2b 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.
AB - 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, IgG1, IgG2a, and IgG2b 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.
KW - Autoimmunity
KW - Lymphotoxin-α
KW - Myasthenia gravis
KW - TNF receptors
KW - TNF-α
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U2 - 10.1016/S0165-5728(01)00474-X
DO - 10.1016/S0165-5728(01)00474-X
M3 - Article
C2 - 11777546
AN - SCOPUS:0036147552
SN - 0165-5728
VL - 122
SP - 85
EP - 93
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -