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

Danling Gu, Lise Wogensen, Nigel A. Calcutt, Chunyao Xia, Simin Zhu, John P. Merlie, Howard S. Fox, Jon Lindstrom, Henry C. Powell, Nora Sarvetnick

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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) γ 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-γ 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.

Original languageEnglish (US)
Pages (from-to)547-557
Number of pages11
JournalJournal of Experimental Medicine
Volume181
Issue number2
DOIs
StatePublished - Feb 1 1995

Fingerprint

Neuromuscular Junction
Myasthenia Gravis
Motor Endplate
Interferons
Transgenic Mice
Cholinesterase Inhibitors
Muscle Weakness
Serum
Autoimmunity
Immunoprecipitation
Paralysis
Autoantibodies
Antigens
Muscles

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Myasthenia gravis-like syndrome induced by expression of interferon γ in the neuromuscular junction. / Gu, Danling; Wogensen, Lise; Calcutt, Nigel A.; Xia, Chunyao; Zhu, Simin; Merlie, John P.; Fox, Howard S.; Lindstrom, Jon; Powell, Henry C.; Sarvetnick, Nora.

In: Journal of Experimental Medicine, Vol. 181, No. 2, 01.02.1995, p. 547-557.

Research output: Contribution to journalArticle

Gu, Danling ; Wogensen, Lise ; Calcutt, Nigel A. ; Xia, Chunyao ; Zhu, Simin ; Merlie, John P. ; Fox, Howard S. ; Lindstrom, Jon ; Powell, Henry C. ; Sarvetnick, Nora. / Myasthenia gravis-like syndrome induced by expression of interferon γ in the neuromuscular junction. In: Journal of Experimental Medicine. 1995 ; Vol. 181, No. 2. pp. 547-557.
@article{223edc341ea1489998c8da247e304c82,
title = "Myasthenia gravis-like syndrome induced by expression of interferon γ in the neuromuscular junction",
abstract = "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) γ 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-γ 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.",
author = "Danling Gu and Lise Wogensen and Calcutt, {Nigel A.} and Chunyao Xia and Simin Zhu and Merlie, {John P.} and Fox, {Howard S.} and Jon Lindstrom and Powell, {Henry C.} and Nora Sarvetnick",
year = "1995",
month = "2",
day = "1",
doi = "10.1084/jem.181.2.547",
language = "English (US)",
volume = "181",
pages = "547--557",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - Myasthenia gravis-like syndrome induced by expression of interferon γ in the neuromuscular junction

AU - Gu, Danling

AU - Wogensen, Lise

AU - Calcutt, Nigel A.

AU - Xia, Chunyao

AU - Zhu, Simin

AU - Merlie, John P.

AU - Fox, Howard S.

AU - Lindstrom, Jon

AU - Powell, Henry C.

AU - Sarvetnick, Nora

PY - 1995/2/1

Y1 - 1995/2/1

N2 - 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) γ 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-γ 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.

AB - 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) γ 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-γ 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.

UR - http://www.scopus.com/inward/record.url?scp=0028906589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028906589&partnerID=8YFLogxK

U2 - 10.1084/jem.181.2.547

DO - 10.1084/jem.181.2.547

M3 - Article

C2 - 7836911

AN - SCOPUS:0028906589

VL - 181

SP - 547

EP - 557

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -