Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by skeletal muscle weakness mainly caused by acetylcholine receptor antibodies. MG can be divided into generalized and ocular, and into early-onset (<50 years of age) and late-onset (≥50 years of age). Anti-Kv1.4 antibodies targeting α-subunits (Kv1.4) of the voltage-gated potassium K+ channel occurs frequently among patients with severe MG, accounting for 18% of a Japanese MG population. The aim of this study was to characterize the clinical features and serological associations of anti-Kv1.4 antibodies in a Caucasian MG population with mild and localized MG. Serum samples from 129 Caucasian MG patients with mainly ocular symptoms were tested for the presence of anti-Kv1.4 antibodies and compared to clinical and serological parameters. There were 22 (17%) anti-Kv1.4 antibody-positive patients, most of them women with late-onset MG, and all of them with mild MG. This contrasts to the Japanese anti-Kv1.4 antibody-positive patients who suffered from severe MG with bulbar symptoms, myasthenic crisis, thymoma, myocarditis and prolonged QT time on electrocardiography, despite equal anti-Kv1.4 antibody occurrence in both populations. No other clinical or serological parameters influenced anti-Kv1.4 antibody occurrence.

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Abbreviations

AChR:

Acetylcholine receptor

ECG:

Electrocardiogram

GMG:

Generalized MG

HSP:

Heat shock protein

Kv1:

Potassium K+ channel α-subunit

MG:

Myasthenia gravis

MMPs:

Matrix metalloproteinases

MRI:

Magnetic resonance imaging

MuSK:

Muscle specific kinase

OMG:

Ocular MG

VGKC:

Voltage-gated potassium K+ channel

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Acknowledgments

This work was supported a grant from the Japanese Ministry of Education, Science, Sports and Culture (no. 23591255) and a Neuroimmunological Disease Research Committee grant from the Japanese Ministry of Health, Labour, and Welfare.

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Correspondence to Fredrik Romi.

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Romi, F., Suzuki, S., Suzuki, N. et al. Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis. J Neurol 259, 1312–1316 (2012). https://doi.org/10.1007/s00415-011-6344-y

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Keywords

  • Myasthenia gravis
  • Anti-Kv1.4 antibodies