Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex.
BACKGROUND
Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes.


RESULTS
In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed. Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain.


CONCLUSIONS
The discovery of antigens such as LGI1 and Caspr2 has resulted in a clinical and molecular definition of the broad group of diseases previously attributed to antibodies against VGKC. Considering the literature that describes the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we propose a practical algorithm for the diagnosis and treatment of these patients.
Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona, Barcelona, España.
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MT
Montojo
Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona, Barcelona, España.
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Petit-Pedrol
Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona, Barcelona, España.
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Graus
Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona, Barcelona, España; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, España. Electronic address: jdalmau@clinic.ub.es.
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J
Dalmau
D001323:Autoantibodies / Q000032:analysis*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011506:Proteins
D001323:Autoantibodies; C403049:CNTNAP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins
Antibodies; Anticuerpos; Autoimmune; Autoinmune; Canales de potasio; Encefalitis; Encephalitis; Potassium channel