A human neural platform for assaying antigen-antibody interactions for autoimmune encephalitis
Autoimmune encephalitides (AE) are a category of diseases that result from an immune attack against proteins present in patient’s own brain cells (antigens). Clinical symptoms include both neurological and psychiatric manifestations, that differ greatly between patients and during disease progression. Upon prompt diagnosis and immunotherapy symptoms gradually resolve. Current epidemiological studies estimate an annual incidence of encephalitis of any aetiology is 2-3 patients per 100.000 per year. However, given that new autoantibodies are being discovered on a half-yearly basis, the incidence of AE is increasing over time and is nowadays comparable to infectious encephalitis. Methods to diagnose AE rely on immunodetection of autoantigens, using rat brain tissue or transfected cells as a source of neural cell surface proteins. Despite being successful in identifying known autoantibodies, in 50% of all AE cases the affected antigen is unknown and cannot be detected using current technologies. Therefore, there is an urgent clinical need for a diagnostic kit that is able to detect all cell surface neuronal antigens. Thanks to the skills acquired during the ERC-StG, we have developed a platform to identify the presence of autoantibodies against neuronal surface antigens in patient serum or CSF using human induced pluripotent stem cell (hiPSC) derived neural cells. Moreover, first experiments validate that our technology can detect an autoantigen in seronegative samples. In the context of this project, we aim to conduct the necessary steps to bring a successful diagnostic approach developed in the bench towards its application as a diagnostic device at the bedside. To this end, we will develop a minimum viable product (MVP), to assess its capability to detect new AE-associated antigens, to distribute it to reference diagnostic laboratories for benchmarking and to explore the possibility of licensing the invention to a third-party company.