In vivo injection of anti-LGI1 antibodies into the rodent M1 cortex and hippocampus is ineffective in inducing seizures.

Autoimmune encephalitis (AIE) associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is the second most common autoimmune encephalitis and is responsible for deleterious neocortical and limbic epileptic seizures. Previous studies demonstrated a pathogenic role of anti-LGI1 antibodies via alterations in the expression and function of Kv1 channels and AMPA receptors. However, the causal link between antibodies and epileptic seizures has never been demonstrated. Here, we attempted to determine the role of human anti-LGI1 autoantibodies in the genesis of seizures by analyzing the impact of their intracerebral injection in rodents. Acute and chronic injections were performed in rats and mice in the hippocampus and primary motor cortex, the two main brain regions affected by the disease. Acute infusion of cerebrospinal fluid or serum IgG of anti-LGI1 AIE patients did not lead to the emergence of epileptic activities, as assessed by multisite electrophysiological recordings over a 10-hour period after injection. A chronic 14-day injection, coupled with continuous video-EEG monitoring, was not more effective. Overall, these results demonstrate that acute and chronic injections of cerebrospinal fluid or purified IgG from LGI1 patients are not able to generate epileptic activity by themselves in the different animal models tested. Significance statement Anti-LGI1 encephalitis is a frequent and severe autoimmune encephalitis. Several previous studies have shown a pathogenic role of anti-LGI1 antibodies, but their link with the emergence of seizures has never been demonstrated. To study the role of anti-LGI1 autoantibodies in the genesis of seizures, we performed acute and chronic injections of cerebrospinal fluid and purified serum IgG of anti-LGI1 encephalitis patients in rodents, targeting the two main brain regions affected by the disease, the hippocampus and primary motor cortex. Brain activities were monitored for 10 hours after acute injections and for 1 month after the beginning of chronic injections. Our results show that chronic and acute injections of anti-LGI1 antibodies were ineffective in inducing epileptic activity in rats and mice.