Myasthenia gravis-like syndrome induced by expression of interferon gamma in the neuromuscular junction

Abnormal humoral responses toward motor end plate constituents in muscle induce myasthenia gravis (MG). To study the etiology of this disease, and whether it could be induced by host defense molecules, we examined the consequences of interferon (IFN) gamma production within the neuromuscular junctio...

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Bibliographic Details
Published in:The Journal of experimental medicine 1995-02, Vol.181 (2), p.547-557
Main Authors: Gu, D, Wogensen, L, Calcutt, N A, Xia, C, Zhu, S, Merlie, J P, Fox, H S, Lindstrom, J, Powell, H C, Sarvetnick, N
Format: Article
Language:English
Subjects:
Animals
Antigens - analysis
Autoimmune Diseases - drug therapy
Autoimmune Diseases - etiology
Autoimmune Diseases - metabolism
Behavior, Animal
Humans
Interferon-gamma - genetics
Interferon-gamma - metabolism
Mice
Mice, Inbred BALB C
Mice, Transgenic
Microscopy, Electron
Muscles - metabolism
Muscles - pathology
Muscles - ultrastructure
Myasthenia Gravis - drug therapy
Myasthenia Gravis - etiology
Myasthenia Gravis - metabolism
Neostigmine - therapeutic use
Neuromuscular Junction - metabolism
Syndrome
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Summary:Abnormal humoral responses toward motor end plate constituents in muscle induce myasthenia gravis (MG). To study the etiology of this disease, and whether it could be induced by host defense molecules, we examined the consequences of interferon (IFN) gamma production within the neuromuscular junction of transgenic mice. The transgenic mice exhibited gradually increasing muscular weakness, flaccid paralysis, and functional disruption of the neuromuscular junction that was reversed after administration of an inhibitor of acetylcholinesterase, features which are strikingly similar to human MG. Furthermore, histological examination revealed infiltration of mononuclear cells and autoantibody deposition at motor end plates. Immunoprecipitation analysis indicated that a previously unidentified 87-kD target antigen was recognized by sera from transgenic mice and also by sera from the majority of human MG patients studied. These results suggest that expression of IFN-gamma at motor end plates provokes an autoimmune humoral response, similar to human MG, thus linking the expression of this factor with development of this disease.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.181.2.547