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Autoimmune channelopathies

Nature Clinical Practice Neurology volume 1, pages 22–33 (2005)Cite this article

Abstract

Autoimmune disorders of the neuromuscular junction remain a paradigm for our understanding of autoimmunity. Since the role of autoantibodies to acetylcholine receptors in the pathogenesis of myasthenia gravis was first recognized in the 1970s, a range of antibody-mediated disorders of the neuromuscular junction have been described, each associated with an autoantibody to a specific ligand-gated receptor, voltage-gated ion channel or related protein. In addition, antibodies to a ganglionic form of acetylcholine receptor have been detected in autoimmune forms of autonomic neuropathy. In the past few years, a role for antibodies in disorders of the CNS has begun to emerge, challenging our previous concepts regarding the blood–brain barrier and the role of the humoral immune system in CNS pathology. Although it has not yet been definitively shown that these CNS conditions are antibody-mediated, the detection of the specific antibody supports a trial of immunosuppressive therapy to which many patients appear to respond. In this article, we review the roles of antibodies to receptors and ion channels in the peripheral and central nervous systems, concentrating on the recently defined autonomic and CNS conditions and on the role of antibody measurement in diagnosis and management.

Key Points

  • The autoimmune channelopathies are neurological disorders in which the patient develops raised serum levels of antibodies to ligand-gated or voltage-gated ion channels, or related proteins

  • Antibodies to acetylcholine receptors are found in 80–85% of patients with generalized myasthenia gravis, and a significant proportion of the remainder have antibodies to muscle-specific kinase. Ganglionic acetylcholine-receptor antibodies are implicated in autoimmune autonomic neuropathies

  • Antibodies to other ligand-gated receptors have been detected in Rasmussen's encephalitis and neuropsychiatric systemic lupus erythematosus

  • Antibodies to voltage-gated calcium channels are associated with Lambert–Eaton myasthenic syndromes and cerebellar ataxia

  • Antibodies to voltage-gated potassium channels are found in acquired neuromyotonia and in various CNS syndromes

  • Immunomodulatory treatments are now being tested in patients with autoimmune channelopathies

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Figure 1: Radioimmunoprecipitation assays for detection of antibodies to ion channels.
Figure 2: Typical structures of a ligand-gated ion channel (acetylcholine receptor), the receptor tyrosine kinase muscle-specific kinase, and voltage-gated channels.
Figure 3: Antibody targets in autoimmune channelopathies.
Figure 4: Coronal T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI of the brain, showing high signal in both hippocampi.

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Authors and Affiliations

  1. Clinical Lecturer in Neurology and A Vincent is Professor of Neuroimmunology at the University of Oxford, Oxford, UK

    Camilla Buckley & Angela Vincent

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  1. Camilla Buckley
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Correspondence to Angela Vincent.

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Competing interests

Angela Vincent and the Department of Clinical Neurology receive payments, royalties and consultancy fees from RSR Ltd who market, and Athena Diagnostics who perform, some of the antibody assays mentioned in this review.

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Buckley, C., Vincent, A. Autoimmune channelopathies. Nat Rev Neurol 1, 22–33 (2005). https://doi.org/10.1038/ncpneuro0033

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