ASPECT-NMO : Measuring autoantigen-specific T cells as new diagnostic sensors and therapeutic targets in neuromyelitis optica

Neuromyelitis optica spectrum of disorders (NMOSD) form a rare group of severe antibody- mediated autoimmune diseases (AID) requiring livelong therapy with severe side effects. The identification of aquaporin-4 (AQP4) as a specific target autoantigen in NMO differentiated it from multiple sclerosis (MS). Autoantigen-specific T cells are centrally involved in the pathogenesis of these diseases via the regulation of pathogenic antibodies. However, their NMOSD-associated phenotypic and functional alterations are still enigmatic. The characterization of autoreactive T cells provides a unique opportunity for the development of novel specific diagnosis and therapies targeting the disease cause rather than the symptoms. Members of our consortium have established powerful technologies for unbiased identification and molecular characterization of autoantigen-specific CD4 T cells. In a proof of principle experiment we identified a unique and discriminative phenotype of ex vivo isolated AQP4-specific T cells in AQP4 antibody positive but not -negative NMOSD patients. We will deeply characterize T cells against AQP4- and myelin oligodendrocyte glycoprotein (MOG) in large NMOSD patient cohorts and screen for cross-reactivity to microbiota as potential pathogenic trigger mechanism. A biotech industry partner will develop analysis tools optimized for rare auto-antigen-specific T cells and for their rapid application in clinical routine. Our project will pursue a unique technical approach to provide a basis for the development of auto-antigen-specific diagnostics and therapeutics.