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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/9994

Title: The Effect of Plasma From Muscle-Specific Tyrosine Kinase Myasthenia Patients on Regenerating Endplates
Authors: ter Beek, W. Pascale
Martinez-Martinez, Pilar
Losen, Mario
Wintzen, Axel R.
Verschuuren, Jan J. G. M.
Niks, Erik H.
van Duinen, Sjoerd G.
Vincent, Angela
Molenaar, Peter C.
Issue Date: 2009
Citation: AMERICAN JOURNAL OF PATHOLOGY, 175(4). p. 1536-1544
Abstract: Muscle-specific tyrosine kinase (MuSK) is essential for clustering of acetylcholine receptors (AChRs) at embryogenesis and likely also important for maintaining synaptic structure in adult muscle. In 5 to 7% of myasthenia gravis (MG) cases, the patients' blood contains antibodies to MuSK. To investigate the effect of MuSK-MG antibody on synapse regeneration, notexin was used to induce damage to the flexor digitorum brevis muscle. We administered aliquots of MuSK-MG patients' plasma to the flexor digitorum brevis twice daily for a period up to 21 days, and muscles were investigated ex vivo in contraction experiments. AChR levels were measured with I-125-alpha-bungarotoxin, and endplates were studied with quantitative immunohistochemistry. in normal muscles and in 14-day regenerated muscles, MuSK plasma caused impairment of nerve stimulus-induced contraction in the presence of 0.35 and 0.5 mmol/L Ca2+ with or without 100 to 400 nmol/L tubocurarine. Endplate size was decreased in regenerated muscles relative to controls; however, we did not observe such differences in muscle not treated with notexin. MuSK plasma had no effect on the amount and turnover rate of AChRs. Our results suggest that anti-MuSK antibodies influence the activity of MuSK molecules without reducing their number, thereby diminishing the size of the endplate and affecting the functioning of AChRs. (Am J Pathol 2009, 175:1536-1544; DOI: 10.2353/ajpath.2009.090040)
Notes: [Martinez-Martinez, Pilar; Losen, Mario; de Baets, Marc H.; Molenaar, Peter C.] Univ Maastricht, Sch Mental Hlth & Neurosci, Dept Neurosci, European Grad Sch Neurosci EURON,Neuroimmunol Grp, NL-6200 MD Maastricht, Netherlands. [ter Beek, W. Pascale; Molenaar, Peter C.] Leiden Univ, Med Ctr, Neurophysiol Sect, Dept Mol Cell Biol, Leiden, Netherlands. [Wintzen, Axel R.; Verschuuren, Jan J. G. M.; Niks, Erik H.; van Duinen, Sjoerd G.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [de Baets, Marc H.] Hasselt Univ, Neuroimmunol Grp, Biomed Res Inst BIOMED, Diepenbeek, Belgium. [Vincent, Angela] Univ Oxford, John Radcliffe Hosp, Neurosci Grp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
URI: http://hdl.handle.net/1942/9994
DOI: 10.2353/ajpath.2009.090040
ISI #: 000270503100020
ISSN: 0002-9440
Category: A1
Type: Journal Contribution
Validation: ecoom, 2010
Appears in Collections: Research publications

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