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

doi:10.1016/j.jneuroim.2015.12.016

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

Research output: Contribution to journal › Article › Academic › peer-review

60 Citations (Scopus)

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 language	English
Pages (from-to)	82-88
Number of pages	7
Journal	Journal of Neuroimmunology
Volume	291
DOIs	https://doi.org/10.1016/j.jneuroim.2015.12.016
Publication status	Published - 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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Longitudinal epitope mapping in MuSK myasthenia gravis_ implications for disease severity
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Huijbers, M. G., Vink, A.-F. D., Niks, E. H., Westhuis, R. H., van Zwet, E. W., de Meel, R. H., Rojas-Garcia, R., Diaz-Manera, J., Kuks, J. B., Klooster, R., Straasheijm, K., Evoli, A., Illa, I., van der Maarel, S. M., & Verschuuren, J. J. (2016). Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity. Journal of Neuroimmunology, 291, 82-88. https://doi.org/10.1016/j.jneuroim.2015.12.016

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title = "Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity",

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.",

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

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doi = "10.1016/j.jneuroim.2015.12.016",

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Huijbers, MG, Vink, A-FD, Niks, EH, Westhuis, RH, van Zwet, EW, de Meel, RH, Rojas-Garcia, R, Diaz-Manera, J, Kuks, JB, Klooster, R, Straasheijm, K, Evoli, A, Illa, I, van der Maarel, SM & Verschuuren, JJ 2016, 'Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity', Journal of Neuroimmunology, vol. 291, pp. 82-88. https://doi.org/10.1016/j.jneuroim.2015.12.016

TY - JOUR

T1 - Longitudinal epitope mapping in MuSK myasthenia gravis

T2 - implications for disease severity

AU - Huijbers, Maartje G.

AU - Vink, Anna-Fleur D.

AU - Niks, Erik H.

AU - Westhuis, Ruben H.

AU - van Zwet, Erik W.

AU - de Meel, Robert H.

AU - Rojas-Garcia, Ricardo

AU - Diaz-Manera, Jordi

AU - Kuks, Jan B.

AU - Klooster, Rinse

AU - Straasheijm, Kirsten

AU - Evoli, Amelia

AU - Illa, Isabel

AU - van der Maarel, Silvere M.

AU - Verschuuren, Jan J.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - 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.

AB - 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.

KW - MuSK

KW - Myasthenia gravis

KW - Neuromuscular junction

KW - Epitope mapping

KW - IgG4

KW - MUSCLE-SPECIFIC KINASE

KW - NEUROMUSCULAR-JUNCTION

KW - COLLAGEN Q

KW - PROTEIN 4

KW - AUTOANTIBODIES

KW - ANTIBODIES

KW - BINDING

KW - IGG4

KW - RECEPTOR

KW - LRP4

U2 - 10.1016/j.jneuroim.2015.12.016

DO - 10.1016/j.jneuroim.2015.12.016

M3 - Article

SN - 0165-5728

VL - 291

SP - 82

EP - 88

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

ER -

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

Abstract

Keywords

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