Are MuSK antibodies the primary cause of myasthenic symptoms?

Duygu Selcen, Taku Fukuda, Xin Ming Shen, Andrew G Engel

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Objective: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). Background: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. Methods: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MuSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. Results: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MuSK reveals one rare and two common DNA polymorphisms. Conclusions: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.

Original languageEnglish (US)
Pages (from-to)1945-1950
Number of pages6
JournalNeurology
Volume62
Issue number11
StatePublished - Jun 8 2004

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Muscle Weakness
Protein-Tyrosine Kinases
Myasthenia Gravis
Cholinergic Receptors
Muscles
Antibodies
Facial Muscles
Respiratory Muscles
Immunoglobulin G
Intercostal Muscles
Masseter Muscle
Diplopia
Palate
Electrophysiology
Tongue
Anti-Idiotypic Antibodies
Electron Microscopy
Nucleotides
Immunohistochemistry
Alleles

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Are MuSK antibodies the primary cause of myasthenic symptoms? / Selcen, Duygu; Fukuda, Taku; Shen, Xin Ming; Engel, Andrew G.

In: Neurology, Vol. 62, No. 11, 08.06.2004, p. 1945-1950.

Research output: Contribution to journalArticle

Selcen, D, Fukuda, T, Shen, XM & Engel, AG 2004, 'Are MuSK antibodies the primary cause of myasthenic symptoms?', Neurology, vol. 62, no. 11, pp. 1945-1950.
Selcen, Duygu ; Fukuda, Taku ; Shen, Xin Ming ; Engel, Andrew G. / Are MuSK antibodies the primary cause of myasthenic symptoms?. In: Neurology. 2004 ; Vol. 62, No. 11. pp. 1945-1950.
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abstract = "Objective: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). Background: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. Methods: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MuSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. Results: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36{\%} decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35{\%} and 55{\%} of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MuSK reveals one rare and two common DNA polymorphisms. Conclusions: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.",
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N2 - Objective: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). Background: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. Methods: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MuSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. Results: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MuSK reveals one rare and two common DNA polymorphisms. Conclusions: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.

AB - Objective: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). Background: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. Methods: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MuSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. Results: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MuSK reveals one rare and two common DNA polymorphisms. Conclusions: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.

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