Pathogenic mechanisms of action of autoantibody-mediated central nervous system disorders targeting neuroglial surface antigens

Autoantibody-mediated diseases targeting central nervous system antigens are increasingly recognised and may manifest as encephalitis or demyelination. A subset of these diseases can be associated with autoantibodies targeting neuronal or glial cell surface proteins (neuroglial surface antibodies or NGsAbs), including leucine-rich glioma inactivated 1, contactin-associated protein-like 2, the N-methyl-D-aspartate receptor, aquaporin-4, and myelin oligodendrocyte glycoprotein, among others. There is accumulating evidence that many NGsAbs may be directly pathogenic, and the associated diseases are responsive to immunotherapy. Underlying disease pathogenesis is still not fully determined and NGsAbs can demonstrate multiple effector mechanisms. In this review, we will briefly outline the clinical syndromes associated with NGsAbs, followed by a detailed breakdown of known in vitro, in vivo and ex vivo studies elucidating pathogenic mechanisms of these autoantibodies. Our understanding of the underlying immunobiology of these conditions ultimately informs more refined therapeutic approaches. • Pathogenic mechanisms of cell surface-targeting neurological antibodies. • In vitro , in vivo and ex vivo models of antibody-mediated CNS autoimmunity. • Pathogenesis of autoantibody-mediated CNS autoimmunity. • Therapeutic advances in autoantibody-mediated CNS autoimmunity.