Anti-AChR antibodies: Mechanisms of action

Anti-AChR antibodies
AChR function: Altered
Post-synaptic membrane: Damage
AChR Degradation: Increased rate
Neuromuscular junction: Normal

Neuromuscular Junction: Normal

From: M Al-Lozi

Normal NMJs

Modulation of post-synaptic AChRs by anti-AChR antibodies

Increased AChR degradation

  • Anti-AChR antibodies cross-link post-synaptic AChRs
  • Cross-linked AChRs are endocytosed more rapidly than normal
  • Internalized AChRs are degraded
  • Fewer AChRs remain on the post-synaptic membrane

  • RESULT: Less efficient neuromuscular transmission

Damage to Post-synaptic Membrane

  • Complement binds to the Antibody-AChR complex
  • Membrane-attack complex (MAC) forms on the membrane
  • The post-junctional membrane is damaged
    • Fewer post-synaptic membrane folds
    • Reduced numbers of AChRs
    • Widened synaptic cleft

  • RESULT: Less efficient neuromuscular transmission

Altered AChR function

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