Furthermore, in animal models, antibodies against MOG can enhance demyelination and inflammation. It is well-known that in experimental autoimmune encephalomyelitis, MOG is a dominant antigen structure after immunization with CNS tissue homogenates ( 25). The exact biological role of MOG remains unclear. MOG, a protein of 245 amino acids, exposed an immunoglobulin domain in the extracellular space and, therefore, seems to be a potential target structure for an autoimmune reaction against myelin. The most promising results came from studies using cell-based assays expressing full-length, conformationally correct folded myelin oligodendrocyte glycoprotein, which is a protein exclusively present in the CNS at the outermost surface of myelin sheaths and oligodendrocyte membranes. Numerous potential antigen targets were studied. However, there is still a lack of biological markers for the identification of multiple sclerosis subtypes, AQP-4-negative neuromyelitis optica spectrum disorder cases, ADEM, and other atypical CNS demyelinating diseases. Knowledge of immunopathogenesis and the diagnostic management changed, and now antibodies against AQP-4 are well integrated in the clinical diagnostic procedures. A breakthrough was the detection of aquaporin-4 (AQP-4) antibodies in neuromyelitis optica spectrum disorder ( 26). Due to diagnostic role of autoantibodies in other autoimmune diseases and evidence for crucial involvement of B cells and antibodies in multiple sclerosis pathogenesis, an international research focus has been directed to antibodies against CNS antigens. In inflammatory demyelinating CNS diseases, it is suggested that an autoimmune reaction finally leading to the cascade of inflammation, demyelination, and axonal loss initiates the development of the disease. Therefore, there is a need for reliable biological markers for diagnostic and prognostic purposes. Despite typical clinical features and paraclinical markers (MRI and cerebrospinal fluid), diagnosis is often challenging. As early treatment initiation is recommended in multiple sclerosis, diagnosis at disease onset is important for patient management and treatment stratification.
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