Autoimmune epilepsy is a rare but increasingly recognised form of drug-resistant epilepsy characterised by frequent seizures in later life. Patients may respond to immune therapy, but causation of disease is poorly understood, and more targeted treatments are required. This gap in knowledge is the major priority for epilepsy specialists, and the area of greatest interest to patients.
In the past year, specific genes in the HLA region have been shown to correlate strongly with LGI1-autoimmune epilepsy. The applicants have replicated and extended these findings in a larger cohort. A striking feature of these genetic findings is the relatively common underlying population frequency of the HLA risk alleles. Therefore, despite the strong link, genetic factors alone do not explain autoimmune epilepsy and there are probably one or more environmental triggers involved. No such factors are known. We hypothesise that gut microbiota are interacting with genetically determined immune factors, to trigger an antigen-specific T-cell response, leading to the development of autoimmune antibody-mediated epilepsy
To test this hypothesis, we will recruit 100 individuals with LGI1-autoimmune epilepsy, and their siblings who haven’t developed the disease. We will collect saliva and stool from each individual, to extract human and bacterial DNA, respectively. Using state of the art DNA sequencing techniques, we will characterise the gut microbiome of people with autoimmune epilepsy and their genetically at risk, yet unaffected siblings. We will compare these profiles to see if the gut microbiome of people with autoimmune epilepsy has a distinctive profile. Identifying an environmental trigger behind autoimmune epilepsy would represent a major step forward both in our understanding of autoimmune epilepsy and also for epilepsy in general, as it would represent the first link between gut microbiota and epilepsy, a link that is increasingly being made for other central nervous system diseases.
