What leads to impairment of neuromuscular transmission in the pathophysiology of myasthenia gravis (MG)?

Updated: Aug 27, 2018
  • Author: Abbas Jowkar, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Antibody response in MG is polyclonal. In an individual patient, antibodies are composed of different subclasses of IgG. In most instances, they are of IgG1 and IgG3 subclass and are directed against the main immunogenic region (MIR) on the alpha subunit. The alpha subunit is also the site of ACh binding, though the binding site for ACh is not always the same as the MIR. Binding of AChR antibodies to AChR results in impairment of neuromuscular transmission in several ways, including the following:

  • Cross-linking 2 adjacent AChRs with anti-AChR antibody, thus accelerating internalization and degradation of AChR molecules

  • Causing complement-mediated destruction of junctional folds of the postsynaptic membrane

  • Blocking the binding of ACh to AChR

  • Decreasing the number of AChRs at the NMJ by simplification of the junctional folds on the postsynaptic membrane, thereby reducing the surface area available for insertion of newly synthesized AChRs


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