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Anti-VGKC-complex encephalitis are caused by antibodies against the voltage gated potassium channel-complex and are implicated in several autoimmune conditions including limbic encephalitis, epilepsy and neuromyotonia.
Research into autoimmune encephalitides have significantly advanced recently. Both tumour associated and nonparaneoplastic conditions are recognized. Different antibodies are more or less selective for different parts of the brain. Antibodies target intracellular antigens in classic paraneoplastic syndromes, but synaptic proteins in nonparaneoplastic conditions. VGKC-complex autoimmune encephalitis is an example of the latter form.
Antibodies directed against VGKC were first reported in neuromyotonia. Further studies led to VGKC antibodies being recognized in Morvan’s syndrome and limbic encephalitis as well. It was for many years erroneously presumed that antibodies detected in a VGKC assay were targeted against the channel itself. But the heterogeneous presentation of patients was difficult to explain. The original assays for the detection of VGKC antibodies used Iodine-125 labelled dendrotoxin and the relatively mild detergent 2% digitonin on mammalian brain homogenate, and VGKC with complexed proteins was extracted. Co-precipitated proteins would thus also be detected in this assay. It’s now acknowledged that most VGKC antibodies are instead directed towards associated/complexed proteins. In a particular study of 96 patients with VGKC antibodies detected with the radioimmunoprecipitation assay, only 3 had antibodies towards the Kv1 subunit of the VGKC channel, 55 had antibodies against Leucine-rich, glioma Inactivated 1 , 19 had antibodies reacting with Contactin-associated protein 2 , 5 had antibodies against Contactin-2 and 18 had antibodies with unknown specificity. Of the patients with Contactin-2 antibodies, 4/5 had antibodies against other antigens as well.