Test for voltage-gated potassium channel (VGKC) autoantibodies is used in the investigation of patients with autoimmune encephalitis and paraneoplastic symptoms.
Autoantibodies against Voltage-Gated Potassium Channel (VGKC) are mainly observed in patients with neuromyotonia, Morvan's syndrome, autoimmune encephalitis, or idiopathic epilepsy. These antibodies are often directed against potassium channel-related proteins such as the CASPR2 protein (Contactin Associated Protein-2), the LGI1 protein (Leucine-rich Glioma Inactivated protein-1), and in very rare cases the Contactin-2 protein. CASPR2, LGI1, and Contactin-2 proteins are considered membrane or extracellular and are important for the function of the potassium channel complex.
Antibodies against the CASPR2 protein are more frequently observed in neuromyotonia and Morvan's syndrome, whereas antibodies against the LGI1 protein are more frequently observed in autoimmune encephalitis. Autoimmune encephalitis is an autoimmune syndrome characterized by episodes of amnesia and seizures. Neuromyotonia is a special condition characterized by a series of fast nerve impulses that lead to muscle contractions and muscle cramps. Morvan's syndrome is similar to neuromyotonia, but the symptoms are accompanied by pain and severe insomnia.
Antibodies against the voltage-gated potassium channels are associated with cancer in approximately 30% of cases of neuromyotonia and in 40% of cases of Morvan's syndrome, with thymoma most common. Tumors are very rare in patients who have VGKC antibodies and autoimmune encephalitis or idiopathic epilepsy.
The method for detecting antibodies against the entire VGKC molecule detects more patients than those detected by testing for autoantibodies against individual CASPR2 and LGI1 antigens. This is probably due to the presence of additional proteins in the VGKC complex that may be related to autoantibodies and possibly that the method used to test VGKC antibodies is more sensitive than the method used to test LGI1 and CASPR2 antibodies.
The VGKC antigen is considered to be an extracellular antigen.