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gMG: An incapacitating, IgG-mediated autoimmune disease1-3

Generalized myasthenia gravis (gMG) is a chronic neuromuscular autoimmune disease driven by pathogenic immunoglobulin G (IgG) autoantibodies against key components of the neuromuscular junction (NMJ).1,4,5

For patients with gMG, the physical and psychological burdens can be severe and life-threatening3,6-8

Muscles

gMG causes intense muscle weakness that often results in impaired mobility, speech, swallowing, and vision, as well as extreme fatigue.3,9

Lungs

Up to 20% of patients experience myasthenic crisis, which can cause fatal respiratory failure.10,11

IgG autoantibodies target multiple components of the NMJ1,4,5

Pathogenic IgG autoantibodies targeting acetylcholine receptors (AChR), muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) have been described in patients with gMG.4,5

stat-achr

of patients have autoantibodies against AChR.5

stat-musk

of patients have autoantibodies against MuSK.4,5

stat-lrp4

of patients have autoantibodies against LRP4.4

stat-autoantibodies

of patients are seronegative, with no identifiable autoantibodies.4

FcRn plays a central role in IgG regulation12,13

The neonatal Fc receptor (FcRn) has been found to recycle IgG and to prolong its half-life, which maintains high concentrations of pathogenic IgG autoantibodies that attack vital components of the NMJ.1,5,12-15
 

When directed against AChR, IgG autoantibodies can often lead to the failure of neuromuscular transmission and skeletal muscle weakness through 3 distinct pathogenic actions.16,17
 

Is it time to take a closer look?

1. Functional blockade of AChR9,16,17

2. Internalization and degradation of AChR9,16,17

3. Activation of the complement system9,16,17

Learn more about the role of IgG autoantibodies and FcRn-mediated IgG recycling in gMG

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References: 1. Rødgaard A et al. Clin Exp Immunol. 1987;67(1):82-88. 2. Jacob S. Eur Neurol Rev. 2018;13(1):18-20. doi.org/10.17925/ENR.2018.13.1.18 3. Twork S et al. Health Qual Life Outcomes. 2010;8:129. doi:10.1186/1477-7525-8-129 4. Gilhus NE. N Engl J Med. 2016;375(26):2570-2581. doi:10.1056/NEJMra1602678 5. Behin A, Le Panse R. J Neuromuscul Dis. 2018;5(3):265-277. doi:10.3233/JND-170294 6. Boldingh MI et al. Health Qual Life Outcomes. 2015;13:115. doi:10.1186/s12955-015-0298-1 7. Eliasen A, Dalhoff KP, Horwitz H. J Neurol. 2018;265(6):1303-1309. doi:10.1007/s00415-018-8837-4 8. Chu HT et al. Front Psychiatry. 2019;10:1-7. doi:10.3389/fpsyt.2019.0048 9. Gilhus NE et al. Nat Rev Neurol. 2016;12(5):259-268. doi:10.1038/nrneurol.2016.44 10. Grob D et al. Muscle Nerve. 2008;37(2):141-149. doi:10.1002/mus.20950 11. Wendell LC, Levine JM. Neurohospitalist. 2011;1(1):16-22. doi:10.1177/1941875210382918 12. Roopenian DC, Akilesh S. Nat Rev Immunol. 2007;7(9):715-725. doi:10.1038/nri2155 13. Ward ES, Ober RJ. Trends Pharmacol Sci. 2018;39(10):892-904. doi:10.1016/j.tips.2018.07.007 14. Ghetie V et al. Eur J Immunol. 1996;26(3):690-696. doi:10.1002/eji.1830260327 15. Ulrichts P et al. J Clin Invest. 2018;128(10):4372-4386. doi:10.1172/JCI97911 16. Huijbers MG et al. J Intern Med. 2014;275(1):12-26. doi:10.1111/joim.12163 17. Mantegazza R et al. Neuropsychiatr Dis Treat. 2011;7:151-160. doi:10.2147/NDT.S8915

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