Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization

Xiaorong Wu; Erdem Tuzun; Jing Li; Tianlin Xiao; Shamsher S. Saini; Huibin Qi; Windy Allman; Premkumar Christadoss

doi:10.1002/mus.22273

Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization

Xiaorong Wu, Erdem Tuzun, Jing Li, Tianlin Xiao, Shamsher S. Saini, Huibin Qi, Windy Allman, Premkumar Christadoss

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Introduction: HLA-DQ8 transgenic mice develop ocular myasthenia gravis (oMG), which then progresses to generalized MG (gMG) when immunized with the human acetylcholine receptor (H-AChR) α subunit. Because the fetal AChR γ subunit is expressed in adult extraocular muscles, we anticipated that γ subunit immunization would generate an immune response to mouse AChR and induce MG in mice. Results: H-AChR γ subunit immunization in HLA-DQ8 mice induced an autoimmune response to mouse AChR and led to the destruction of AChR in the neuromuscular junction (NMJ) by anti-AChR antibody and complement activation, and it triggered upregulation of AChR gene transcription. Conclusion: Our findings indicate that oMG may be induced by immunity to the AChR γ subunit.

Original language	English (US)
Pages (from-to)	209-216
Number of pages	8
Journal	Muscle and Nerve
Volume	45
Issue number	2
DOIs	https://doi.org/10.1002/mus.22273
State	Published - Feb 2012
Externally published	Yes

Keywords

Acetylcholine receptor γ subunit
Autoimmune disease
Extraocular muscles
Myasthenia gravis
Ocular myasthenia gravis

ASJC Scopus subject areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

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10.1002/mus.22273

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title = "Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization",

abstract = "Introduction: HLA-DQ8 transgenic mice develop ocular myasthenia gravis (oMG), which then progresses to generalized MG (gMG) when immunized with the human acetylcholine receptor (H-AChR) α subunit. Because the fetal AChR γ subunit is expressed in adult extraocular muscles, we anticipated that γ subunit immunization would generate an immune response to mouse AChR and induce MG in mice. Results: H-AChR γ subunit immunization in HLA-DQ8 mice induced an autoimmune response to mouse AChR and led to the destruction of AChR in the neuromuscular junction (NMJ) by anti-AChR antibody and complement activation, and it triggered upregulation of AChR gene transcription. Conclusion: Our findings indicate that oMG may be induced by immunity to the AChR γ subunit.",

keywords = "Acetylcholine receptor γ subunit, Autoimmune disease, Extraocular muscles, Myasthenia gravis, Ocular myasthenia gravis",

author = "Xiaorong Wu and Erdem Tuzun and Jing Li and Tianlin Xiao and Saini, \{Shamsher S.\} and Huibin Qi and Windy Allman and Premkumar Christadoss",

year = "2012",

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doi = "10.1002/mus.22273",

language = "English (US)",

volume = "45",

pages = "209--216",

journal = "Muscle and Nerve",

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TY - JOUR

T1 - Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization

AU - Wu, Xiaorong

AU - Tuzun, Erdem

AU - Li, Jing

AU - Xiao, Tianlin

AU - Saini, Shamsher S.

AU - Qi, Huibin

AU - Allman, Windy

AU - Christadoss, Premkumar

PY - 2012/2

Y1 - 2012/2

N2 - Introduction: HLA-DQ8 transgenic mice develop ocular myasthenia gravis (oMG), which then progresses to generalized MG (gMG) when immunized with the human acetylcholine receptor (H-AChR) α subunit. Because the fetal AChR γ subunit is expressed in adult extraocular muscles, we anticipated that γ subunit immunization would generate an immune response to mouse AChR and induce MG in mice. Results: H-AChR γ subunit immunization in HLA-DQ8 mice induced an autoimmune response to mouse AChR and led to the destruction of AChR in the neuromuscular junction (NMJ) by anti-AChR antibody and complement activation, and it triggered upregulation of AChR gene transcription. Conclusion: Our findings indicate that oMG may be induced by immunity to the AChR γ subunit.

AB - Introduction: HLA-DQ8 transgenic mice develop ocular myasthenia gravis (oMG), which then progresses to generalized MG (gMG) when immunized with the human acetylcholine receptor (H-AChR) α subunit. Because the fetal AChR γ subunit is expressed in adult extraocular muscles, we anticipated that γ subunit immunization would generate an immune response to mouse AChR and induce MG in mice. Results: H-AChR γ subunit immunization in HLA-DQ8 mice induced an autoimmune response to mouse AChR and led to the destruction of AChR in the neuromuscular junction (NMJ) by anti-AChR antibody and complement activation, and it triggered upregulation of AChR gene transcription. Conclusion: Our findings indicate that oMG may be induced by immunity to the AChR γ subunit.

KW - Acetylcholine receptor γ subunit

KW - Autoimmune disease

KW - Extraocular muscles

KW - Myasthenia gravis

KW - Ocular myasthenia gravis

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JO - Muscle and Nerve

JF - Muscle and Nerve

IS - 2

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Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization

Abstract

Keywords

ASJC Scopus subject areas

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