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

Maartje G. Huijbers*, Anna-Fleur D. Vink, Erik H. Niks, Ruben H. Westhuis, Erik W. van Zwet, Robert H. de Meel, Ricardo Rojas-Garcia, Jordi Diaz-Manera, Jan B. Kuks, Rinse Klooster, Kirsten Straasheijm, Amelia Evoli, Isabel Illa, Silvere M. van der Maarel, Jan J. Verschuuren

*Corresponding author for this work

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    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. (C) 2016 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)82-88
    Number of pages7
    JournalJournal of Neuroimmunology
    Volume291
    DOIs
    Publication statusPublished - 15-Feb-2016

    Keywords

    • MuSK
    • Myasthenia gravis
    • Neuromuscular junction
    • Epitope mapping
    • IgG4
    • MUSCLE-SPECIFIC KINASE
    • NEUROMUSCULAR-JUNCTION
    • COLLAGEN Q
    • PROTEIN 4
    • AUTOANTIBODIES
    • ANTIBODIES
    • BINDING
    • IGG4
    • RECEPTOR
    • LRP4

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