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

• Published in: Muscle & nerve 2012-02, Vol.45 (2), p.209-216
• Main Authors: Wu, Xiaorong, Tuzun, Erdem, Li, Jing, Xiao, Tianlin, Saini, Shamsher S., Qi, Huibin, Allman, Windy, Christadoss, Premkumar
• Format: Article
• Language: English
• 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
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.22273

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