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LGI1 Appears to Be Autoantigen Linked to Limbic Encephalitis

Voltage-gated potassium channels previously thought to be target of autoantibodies

TUESDAY, June 29 (HealthDay News) -- The target of autoantibodies associated with limbic encephalitis previously thought to be voltage-gated potassium channels is actually leucine-rich, glioma-inactivated 1 protein (LGI1), which serves as a ligand for two epilepsy-related proteins, according to a study published online June 28 in The Lancet Neurology.

Meizan Lai, M.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues evaluated sera samples and cerebrospinal fluid (CSF) of 57 patients with limbic encephalitis and antibodies attributed to voltage-gated potassium channels, as well as 148 control individuals who had other disorders with or without antibodies against voltage-gated potassium channels.

The researchers found that all patients tested had antibodies against LGI1, but not to potassium channels. LGI1 was established as the autoantigen of limbic encephalitis using several experiments, including immunoprecipitation of LGI1 with patient's antibodies, immunostaining of HEK293 cells expressing LGI1 with sera and CSF from patients, specific abrogation of patients' sera and CSF brain reactivity after immunoabsorption with LGI1-expressing cells, and comparative brain immunostaining.

"LGI1 is the autoantigen associated with limbic encephalitis previously attributed to voltage-gated potassium channels," the authors write. "The term limbic encephalitis associated with antibodies against voltage-gated potassium channels should be changed to limbic encephalitis associated with LGI1 antibodies, and this disorder should be classed as an autoimmune synaptic encephalopathy."

The study was partly funded by Euroimmun. One author submitted a patent application in the United States for the use of LGI1 antibody determination in patients' sera and CSF as a diagnostic test.

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