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Topic: Autoimmune neurological diseases associated with
Review
autoantibodies specific for synaptic antigens

Neurological diseases associated with

autoantibodies targeting the voltage‑gated

potassium channel complex: immunobiology and

clinical characteristics

Domenico Plantone, Rosaria Renna, Tatiana Koudriavtseva

Multiple Sclerosis Center, Unit of Neurology, Regina Elena National Cancer Institute, 00144 Rome, Italy.

A B S T R AC T
Voltage‑gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including
modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of
the action potential. VGKCs are complexed with other neuronal proteins, and it is now widely known that serum autoantibodies
directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients. By contrast,
these autoantibodies more commonly target three proteins that are complexed with alpha‑dendrotoxin‑labeled potassium channels
in brain extracts. These three proteins are contactin‑associated protein‑2 (Caspr‑2), leucine‑rich, glioma inactivated 1 (LGI‑1)
protein and the protein Tag‑1/contactin‑2. Neoplasms are detected only in a minority of seropositive patients for VGKC
complex‑IgG and do not significantly associate with Caspr‑2 or LGI‑1. Among all the cancers described in association with VGKC
complex‑IgG, lung carcinoma, thymoma, and hematologic malignancies are the most commonly detected. We will review all
the major neurological conditions associated with VGKC complex‑IgG. These include Isaacs’ syndrome, Morvan syndrome,
limbic encephalitis, facio‑brachial dystonic seizures, chorea and other movement disorders, epilepsy, psychosis, gastrointestinal
neuromuscular diseases, a subacute encephalopathy that mimics Creutzfeldt‑Jakob prion disease both clinically and radiologically
and autoimmune chronic pain. The vast majority of these conditions are reversible by immunotherapy, and it is becoming
increasingly recognized that early diagnosis and detection of VGKC complex‑IgG is critical in order to rapidly start the treatment.
As a result, VGKC complex‑IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy, memory
or cognitive problems, or peripheral nerve hyperexcitability syndromes.
Key words: Chronic pain, epilepsy；facio‑brachial dystonic seizures；leucine‑rich glioma inactivated 1 protein; limbic encephalitis;
movement disorders; neuromyotonia; voltage‑gated potassium channels

INTRODUCTION notably the “Shaker” type Kv1 channels (Kv1.1,
Kv1.2, Kv1.6), sensitive to alpha‑dendrotoxin.
[2]
Voltage‑gated potassium channels (VGKCs) represent VGKCs are complexed with other neuronal
a group of tetrameric signaling proteins with several proteins, and it is now widely known that serum
functions, including modulation of neuronal excitability autoantibodies directed against VGKCs are actually
and neurotransmitter release. Moreover, VGKCs directed against the potassium channel subunits
[1]
contribute to the generation of the action potential. only in a minority of patients. In contrast, these
Neurological autoimmune and paraneoplastic autoantibodies more commonly target three proteins
syndromes involve only a small number of VGKCs, that are complexed with alpha‑dendrotoxin‑labeled
potassium channels in brain extracts. These
[3]
Corresponding Author: Dr. Domenico Plantone, Multiple
Sclerosis Center, Unit of Neurology, Regina Elena National three proteins are contactin‑associated protein‑2
Cancer Institute, IFO, Via Elio Chianesi 53, 00144 Rome, Italy.
E‑mail: domenicoplantone@hotmail.com This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
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Cite this article as: Plantone D, Renna R, Koudriavtsev T. Neurological
diseases associated with autoantibodies targeting the voltage-gated
potassium channel complex: immunobiology and clinical characteristics
DOI: 2016;3:69-78.
10.4103/2347-8659.169883
Received: 01-01-2015; Accepted: 31-03-2015

© 2016 Neuroimmunology and Neuroinflammation | Published by OAE Publishing Inc. 69