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Identification of autoantigens in demyelinating diseases is essential for the understanding of the pathogenesis. Immune responses against these antigens could be used as biomarkers for diagnosis, prognosis and treatment responses. Knowledge of antigen-specific immune responses in individual patients is also a prerequisite for antigen-based therapies.A proportion of patients with demyelinating disease have antibodies to aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG). Patients with anti-AQP4 have the distinct clinical presentation of neuromyelitis optica (NMO), and these patients often also harbour other autoimmune responses. In contrast, anti-MOG is seen in patients with different disease entities such as childhood multiple sclerosis (MS), acute demyelinating encephalomyelitis (ADEM), anti-AQP4 negative NMO, and optic neuritis, but hardly in adult MS. A number of new candidate autoantigens have been identified and await validation. Antigen-based therapies are mainly aimed at tolerizing T-cell responses against myelin basic protein (MBP) and have shown only modest or no clinical benefit so far.Currently, only few patients with demyelinating diseases can be characterized based on their autoantibody profile. The most prominent antigens in this respect are MOG and AQP4. Further research has to focus on the validation of newly discovered antigens as biomarkers.