Chapter 99 : Myasthenia Gravis

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Myasthenia gravis (MG) is a disease of striated muscles which clinically manifests as weakness. It is caused by impaired neuromuscular transmission due to a reduction in the number of receptors for the neurotransmitter acetylcholine (ACh) at the postsynaptic myoneural junction. This reduction is caused predominantly by the action of anti-acetylcholine receptor (anti-AChR) antibodies in most instances. The disease occurs with a reported prevalence of 0.5 to 5/100,000 and an incidence of 0.4/100,000/year. MG can occur at any age; however, it typically presents in the second and third decades of life, with a later peak occurring after age 50 (late-onset disease). A female preponderance (3:1 to 4:1) has been reported in the first 40 years of life; thereafter, the incidences are comparable between the sexes.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
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Image of FIGURE 1

The AChR. The subunits of the AChR—α, β, δ, and γ or ε—are arranged like barrel staves around the central ion pore. Each subunit winds through the junctional membrane four times (sites M1, M2, M3, and M4). In the unfolded view of the α subunit, the amino-terminal end of the α subunit is extracellular, where it is accessible to ACh, which binds at the site shown (amino acids 192 and 193). In MG, autoantibodies may bind to various epitopes of all subunits, but a high proportion of antibodies bind to the main immunogenic region of the α subunit.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
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Image of FIGURE 2

Schematic representation of the myoneural junction. Vesicles of ACh release their contents at active zones across from AChRs in response to impulses conducted down nerve axons. ACh diffuses across the synaptic cleft and binds to AChRs when not interdicted by AChE, with opening of the ion channel and the generation of endplate potentials. Action potential is propagated to muscle when sufficient amplitude of summated endplate potentials is attained. MuSK is a neuromuscular protein that anchors AChRs to the muscle membrane. LRP4 is a receptor for agrin, which activates clustering of MuSK and AChRs.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
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