Fast Five Quiz: Pathophysiology of Myasthenia Gravis

Raghav Govindarajan, MD; Nicholas J. Silvestri, MD

Disclosures

September 15, 2023

Isolation of MuSK autoantibody-producing B cells is challenging because they reside more in the lymphatics, bone marrow or other tissue than in the circulation, but B cells have been found in the circulation and have a phenotype of memory B cells or short-lived plasmablasts. MuSK MG develops via autoantibodies with the IgG subclass IgG4 — which, unlike other subclasses, can undergo Fab-arm exchange — thereby directly disrupting AChR signalling by hindering NMJ protein-protein interactions.

The mechanism used by B cells for autoantibody production differs between AChR MG and MuSK MG. AChR MG is characterised by the complement-activating IgG subclasses IgG1, IgG2 and IgG3, produced by plasma cells residing in tissues such as the bone marrow and thymus, with effector functions that can cause tissue damage at the NMJ. Also, unlike MuSK MG, AChR-specific autoantibodies stem from long-lived plasma cells.

Learn more about the pathophysiology of MG.

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