Tumor associations Principally thymoma
(around 20%) and small cell lung cancer (<5%). Most cases do not
have a tumour.
Frequency of anti-VGKC antibodies in patients with
appropriate clinical syndromes without evidence of cancer is high (>80%)
Screening test:
High titres of VGKC antibodies may be detected by immunohistochemistry
showing characteristic staining of molecular layer of the cerebellum
(Fig 1a), or hippocampus (Fig 1b). These should be confirmed by immunoprecipitation
assay using 125I-dendrotoxin-labelled VGKCs extracted from human or
rodent brain tissue. Lower titres of VGKC antibodies are only detected
by this immunoprecipitation assay. This assay only measures antibodies
to the dendrotoxin-binding Kv1.1, 1.2 and 1.6 forms of VGKCs.
Figure 1a. (Taken
from Vincent et al Brain 2004). Rat cerebellum immunoreacted with
a VGKC- antibody- positive serum. ML: molecular layer, PC: Purkinje
cell; GL: granular layer.
Figure 1b (Courtesy of Dr Camilla
Buckley). Rat hippocampus immunoreacted with a VGKC- antibody- positive
serum
Confirmatory test:
No commercial tests or recombinant proteins available currently.
Immunologic associations:
Patients with VGKC antibodies may have associated myasthenia gravis
with or without acetylcholine receptor antibodies, or may have acetylcholine
receptor antibodies without myasthenia gravis. Other thymoma-related
antibodies (eg. Interferon alpha, IL-12) may be present. Acquired neuromyotonia
has been reported in patients following bone marrow transfer, with systemic
sclerosis and with other autoimmune diseases.
VGKCs
VGKCs are a family of voltage-gated shaker-like potassium channels.
They are membrane proteins and responsible for controlling the cell
membrane potential. They are made up of tetramers and are usually hetero-tetramers
of different subtypes. Dendrotoxin binds to Kv1.1, 1.2 and 1.6 principally,
and therefore it is thought that these subtypes are the most likely
targets for the VGKC antibodies. VGKCs are expressed by a wide range
of different cells, but are most important in the control of membrane
excitability in the nervous system.
References
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Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. Phenotypic
variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;
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Liguori R, Vincent A, Clover L, Avoni P, Plazzi G, Cortelli P,
et al. Morvan's syndrome: peripheral and central nervous system and
cardiac involvement with antibodies to voltage-gated potassium channels.
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Pozo-Rosich P, Clover L, Saiz A, Vincent A, Graus F. Voltage-gated
potassium channel antibodies in idiopathic and paraneoplastic limbic
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Wang H, Kunkel DD, Schwartzkroin PA, Tempel BL. Localization of
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and dendrites in the mouse brain. J Neurosci 1994; 14: 4588-99.
Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, Detert N, et
al. Potassium channel antibody-associated encephalopathy: a potentially
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