General Principles of Neuronal and Glial Antibodies in Demyelinating and Encephalitic Disorders

Over the last 20 years antibodies to cell surface neuronal and glial proteins have been discovered in patients with immunotherapy-responsive disorders.  Accordingly, the field of antibody-mediated CNS disorders has become a focus for much clinical and experimental research.  The antigenic targets are largely membrane proteins that are often complex and multi-subunit and the best antibody detection techniques are cell-based assays (CBAs).  In CBAs, the proteins are expressed in cell lines, usually the human embryonic kidney (HEK) cells, and the patient’s serum or cerebrospinal fluid are applied to the live, or sometimes fixed, cells.  Antibody binding is detected by indirect immunofluorescence.    Antibodies to a number of receptors and ion-channel related proteins have been detected in forms of autoimmune encephalitis or encephalomyelitis.  Similar techniques are used to detect antibodies to aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) in patients with demyelinating disorders.  Although the targets of the antibodies generally relate well to the clinical features of the patients, there are some intriguing aspects.  For instance, NMDA (glutamate) receptor antibodies have been found occasionally in patients with white matter lesions, and it is now well established that MOG antibodies can involve grey as well as white matter disease.

In principle, the pathogenicity of antibodies should be demonstrated by in vitro and in vivo approaches.  The talk will demonstrate the methodologies and results regarding antibody-detection, in vitro and in vivo results of different antibodies.