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Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization
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 subun...
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| Published in: | Muscle & nerve 2012-02, Vol.45 (2), p.209-216 |
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| container_issue | 2 |
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| container_title | Muscle & nerve |
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| creator | Wu, Xiaorong Tuzun, Erdem Li, Jing Xiao, Tianlin Saini, Shamsher S. Qi, Huibin Allman, Windy Christadoss, Premkumar |
| description | 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. Muscle Nerve, 2012 |
| doi_str_mv | 10.1002/mus.22273 |
| format | article |
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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. Muscle Nerve, 2012</description><identifier>ISSN: 0148-639X</identifier><identifier>EISSN: 1097-4598</identifier><identifier>DOI: 10.1002/mus.22273</identifier><identifier>PMID: 22246876</identifier><identifier>CODEN: MUNEDE</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>acetylcholine receptor γ subunit ; Animals ; Antibodies, Anti-Idiotypic - blood ; Antibodies, Anti-Idiotypic - immunology ; Arabidopsis Proteins - metabolism ; autoimmune disease ; Biological and medical sciences ; Cell Proliferation ; Complement C3 - metabolism ; Disease Models, Animal ; Diseases of striated muscles. Neuromuscular diseases ; Enzyme-Linked Immunosorbent Assay ; extraocular muscles ; Fundamental and applied biological sciences. Psychology ; HLA-DQ Antigens - genetics ; Humans ; Immunization - adverse effects ; Intramolecular Transferases - metabolism ; Lymphocyte Activation - immunology ; Medical sciences ; Mice ; Mice, Transgenic ; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration ; Muscle Strength - genetics ; myasthenia gravis ; Myasthenia Gravis, Autoimmune, Experimental - blood ; Myasthenia Gravis, Autoimmune, Experimental - etiology ; Myasthenia Gravis, Autoimmune, Experimental - genetics ; Myasthenia Gravis, Autoimmune, Experimental - pathology ; Neurology ; Neuromuscular Junction - immunology ; Ocular Motility Disorders - etiology ; Ocular Motility Disorders - immunology ; ocular myasthenia gravis ; Protein Subunits - genetics ; Protein Subunits - metabolism ; Receptors, Nicotinic - immunology ; Vertebrates: nervous system and sense organs</subject><ispartof>Muscle & nerve, 2012-02, Vol.45 (2), p.209-216</ispartof><rights>Copyright © 2011 Wiley Periodicals, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3073-56112a03bee1a71e9642a361df038290d5e2214aaf2070e51ea5cef1dcfb2db33</citedby><cites>FETCH-LOGICAL-c3073-56112a03bee1a71e9642a361df038290d5e2214aaf2070e51ea5cef1dcfb2db33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25506547$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22246876$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Xiaorong</creatorcontrib><creatorcontrib>Tuzun, Erdem</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Xiao, Tianlin</creatorcontrib><creatorcontrib>Saini, Shamsher S.</creatorcontrib><creatorcontrib>Qi, Huibin</creatorcontrib><creatorcontrib>Allman, Windy</creatorcontrib><creatorcontrib>Christadoss, Premkumar</creatorcontrib><title>Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization</title><title>Muscle & nerve</title><addtitle>Muscle Nerve</addtitle><description>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. Muscle Nerve, 2012</description><subject>acetylcholine receptor γ subunit</subject><subject>Animals</subject><subject>Antibodies, Anti-Idiotypic - blood</subject><subject>Antibodies, Anti-Idiotypic - immunology</subject><subject>Arabidopsis Proteins - metabolism</subject><subject>autoimmune disease</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Complement C3 - metabolism</subject><subject>Disease Models, Animal</subject><subject>Diseases of striated muscles. Neuromuscular diseases</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>extraocular muscles</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HLA-DQ Antigens - genetics</subject><subject>Humans</subject><subject>Immunization - adverse effects</subject><subject>Intramolecular Transferases - metabolism</subject><subject>Lymphocyte Activation - immunology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration</subject><subject>Muscle Strength - genetics</subject><subject>myasthenia gravis</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - blood</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - etiology</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - genetics</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - pathology</subject><subject>Neurology</subject><subject>Neuromuscular Junction - immunology</subject><subject>Ocular Motility Disorders - etiology</subject><subject>Ocular Motility Disorders - immunology</subject><subject>ocular myasthenia gravis</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - metabolism</subject><subject>Receptors, Nicotinic - immunology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0148-639X</issn><issn>1097-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp10M9u1DAQBnALgehSOPACyBeEOKT1n9hOjlBBQVqoKihwsybOpGtInMWOgfS1eA-eicBuy4nTHOb3zUgfIQ85O-KMieMhpyMhhJG3yIqz2hSlqqvbZMV4WRVa1p8OyL2UPjPGeKXNXXKw4FJXRq_I5szlHiKF0NJLDBih91fY0mGGNG0weKCXEb75RH1os1s2zUw3eYBAweE0924z9j4gjehwO42R_vpJU25y8BP1w7DMK5j8GO6TOx30CR_s5yG5ePni_cmrYn12-vrk2bpwkhlZKM25ACYbRA6GY61LAVLztmOyEjVrFQrBS4BOMMNQcQTlsOOt6xrRNlIekie7u9s4fs2YJjv45LDvIeCYk625VoJxrRf5dCddHFOK2Nlt9APE2XJm__Rql17t314X-2h_NTcDtjfyusgFPN4DSA76LkJwPv1zSjGtSrO445377nuc___Rvrl4d_262CV8mvDHTQLiF6uNNMp-fHtqz9W6_GCea3sufwNbtKDX</recordid><startdate>201202</startdate><enddate>201202</enddate><creator>Wu, Xiaorong</creator><creator>Tuzun, Erdem</creator><creator>Li, Jing</creator><creator>Xiao, Tianlin</creator><creator>Saini, Shamsher S.</creator><creator>Qi, Huibin</creator><creator>Allman, Windy</creator><creator>Christadoss, Premkumar</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201202</creationdate><title>Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization</title><author>Wu, Xiaorong ; Tuzun, Erdem ; Li, Jing ; Xiao, Tianlin ; Saini, Shamsher S. ; Qi, Huibin ; Allman, Windy ; Christadoss, Premkumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3073-56112a03bee1a71e9642a361df038290d5e2214aaf2070e51ea5cef1dcfb2db33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>acetylcholine receptor γ subunit</topic><topic>Animals</topic><topic>Antibodies, Anti-Idiotypic - blood</topic><topic>Antibodies, Anti-Idiotypic - immunology</topic><topic>Arabidopsis Proteins - metabolism</topic><topic>autoimmune disease</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation</topic><topic>Complement C3 - metabolism</topic><topic>Disease Models, Animal</topic><topic>Diseases of striated muscles. Neuromuscular diseases</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>extraocular muscles</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HLA-DQ Antigens - genetics</topic><topic>Humans</topic><topic>Immunization - adverse effects</topic><topic>Intramolecular Transferases - metabolism</topic><topic>Lymphocyte Activation - immunology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration</topic><topic>Muscle Strength - genetics</topic><topic>myasthenia gravis</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - blood</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - etiology</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - genetics</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - pathology</topic><topic>Neurology</topic><topic>Neuromuscular Junction - immunology</topic><topic>Ocular Motility Disorders - etiology</topic><topic>Ocular Motility Disorders - immunology</topic><topic>ocular myasthenia gravis</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - metabolism</topic><topic>Receptors, Nicotinic - immunology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Xiaorong</creatorcontrib><creatorcontrib>Tuzun, Erdem</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Xiao, Tianlin</creatorcontrib><creatorcontrib>Saini, Shamsher S.</creatorcontrib><creatorcontrib>Qi, Huibin</creatorcontrib><creatorcontrib>Allman, Windy</creatorcontrib><creatorcontrib>Christadoss, Premkumar</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Muscle & nerve</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Xiaorong</au><au>Tuzun, Erdem</au><au>Li, Jing</au><au>Xiao, Tianlin</au><au>Saini, Shamsher S.</au><au>Qi, Huibin</au><au>Allman, Windy</au><au>Christadoss, Premkumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization</atitle><jtitle>Muscle & nerve</jtitle><addtitle>Muscle Nerve</addtitle><date>2012-02</date><risdate>2012</risdate><volume>45</volume><issue>2</issue><spage>209</spage><epage>216</epage><pages>209-216</pages><issn>0148-639X</issn><eissn>1097-4598</eissn><coden>MUNEDE</coden><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. Muscle Nerve, 2012</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22246876</pmid><doi>10.1002/mus.22273</doi><tpages>8</tpages></addata></record> |
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| subjects | acetylcholine receptor γ subunit Animals Antibodies, Anti-Idiotypic - blood Antibodies, Anti-Idiotypic - immunology Arabidopsis Proteins - metabolism autoimmune disease Biological and medical sciences Cell Proliferation Complement C3 - metabolism Disease Models, Animal Diseases of striated muscles. Neuromuscular diseases Enzyme-Linked Immunosorbent Assay extraocular muscles Fundamental and applied biological sciences. Psychology HLA-DQ Antigens - genetics Humans Immunization - adverse effects Intramolecular Transferases - metabolism Lymphocyte Activation - immunology Medical sciences Mice Mice, Transgenic Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration Muscle Strength - genetics myasthenia gravis Myasthenia Gravis, Autoimmune, Experimental - blood Myasthenia Gravis, Autoimmune, Experimental - etiology Myasthenia Gravis, Autoimmune, Experimental - genetics Myasthenia Gravis, Autoimmune, Experimental - pathology Neurology Neuromuscular Junction - immunology Ocular Motility Disorders - etiology Ocular Motility Disorders - immunology ocular myasthenia gravis Protein Subunits - genetics Protein Subunits - metabolism Receptors, Nicotinic - immunology Vertebrates: nervous system and sense organs |
| title | Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization |
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