VGKC (voltage gated potassium channel) antibodies

Indication

Suspicion of autoimmune encephalitis and paraneoplastic symptoms.

Method

Radioimmunoprecipitation (RIA).

Answer

The result is reported as negative or positive with a value (pmol/L).

Interpretation

Autoantibodies directed against VGKC are primarily seen in patients with neuromyotonia, Morvans syndrome, autoimmune encephalitis or idiopathic epilepsy. These antibodies are often directed against the potassium channel-associated proteins CASPR2 (contactin associated protein-2) and LGI1 (leucine rich glioma inactivated protein-1) and in very rare cases against Contactin-2. CASPR2, LGI1 and Contactin-2 proteins count as membranes associated or extracellular and are important for co-localization of the Potassium Channel complex.

Antibodies against CASPR2 are more commonly seen in neuromyotonia and Morvans syndrome, while antibodies to LGI1 are more commonly seen in autoimmune encephalitis. Autoimmune encephalitis (AE) is an autoimmune syndrome that is characterized by interference with episodic memory and epileptic seizures. Neuromyotonia is a special condition characterized by the fact that series of fast nerve impulses lead to muscle twitching and muscle cramps. Morvans syndrome resembles neuromyotonia where symptoms are associated with pain and severe insomnia.

Antibodies against VGKC have been reported to be associated with cancer in approximately 30% of cases with neuromyotonia and 40% of Morvans syndrome cases. Tymom is most common. Tumors are very rare in patients who have VGKC antibodies and associated autoimmune encephalitis or idiopathic epilepsy.

The method for VGKC antibody detection detects more autoantibodys positive patients than detected by the CASPR2 and LGI1 autoantibody assays. This is probably due to the presence of additional proteins in the VGKC complex that may be associated with autoantibodies (i.e., more antigen is included in the VGKC complex) and possibly that the RIA method used for VGKC analysis is more sensitive than the indirect immunofluorescence method used for LGI1 and CASPR2.

The relevance of autoantibodies with levels below 300 pmol/L is doubtful. In autoimmune encephalitis, the antibody level is often over 300-500 pmol/L.

VGKC is seen as an extracellular antigen. Generally, treatment with immunotherapy is more effective at autoantibodies directed against extracellular antigens than autoantibodies against intracellular antigens.

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References

Hart et al. (1997). Autoantibodies detected to expressed K+ channels are implicated in Neuromyotonia. Ann Neurol 41: 238-246. PMID: 9029073.

Vincent A. et al. (2004). Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 127: 701-712. PMID: 14960497.

Tan K. et al. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 70:1883-1890. PMID: 18474843.

Harrower T. et al. (2006). A case of voltage-gated potassium channel antibody-related limbic encephalitis. Nature 2:6:339-343. PMID: 16932578.

Irani S. et al. (2010).Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvans syndrome and acquired neuromyotonia. Brain. 2010 Sep;133(9):2734-2748. PMID: 20663977.

Olberg H. et. al. Neurological manifestations related to level of voltage-gated potassium channel antibodies. J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):941-943. PMID: 23595945.

Packages and other tests

View other packages Paraneoplastic Syndromes and Limbic Encephalitis (560, 561 and 562). View other tests VGCC (voltage-gated calcium channel) antibodies

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