Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity

J Neuroimmunol. 2016 Feb 15;291:82-8. doi: 10.1016/j.jneuroim.2015.12.016. Epub 2016 Jan 5.


Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies.

Keywords: Epitope mapping; IgG4; MuSK; Myasthenia gravis; Neuromuscular junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Cholinesterase Inhibitors / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping*
  • Female
  • Humans
  • Italy
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myasthenia Gravis / blood*
  • Myasthenia Gravis / drug therapy
  • Myasthenia Gravis / immunology*
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Cholinergic / immunology*
  • Severity of Illness Index
  • Spain
  • Statistics as Topic
  • Young Adult


  • Autoantibodies
  • Cholinesterase Inhibitors
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases