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

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

Author information

1
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands. Electronic address: M.G.M.Huijbers@lumc.nl.
2
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
3
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
4
Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands.
5
Department of Neurology, Hospital Santa Creu I Sant Pau, Barcelona, Spain.
6
Department of Neurology, University Medical Centre Groningen, Groningen, The Netherlands.
7
Department of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy.

Abstract

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

PMID:
26857500
DOI:
10.1016/j.jneuroim.2015.12.016
[Indexed for MEDLINE]

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