Neuroglia in autoimmune encephalitis

Neuroglial cells play a crucial role in central nervous system (CNS) health and disease. Antibody-associated autoimmune encephalitis (AE) represents a group of inflammatory brain diseases with antibodies (Abs) against neuronal cell surface (e.g., anti-N-methyl-d-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid (GABA) type A or B receptor (GABA_A/BR)) or intracellular neuronal proteins. AE with Abs against glial antigens, e.g., myelin oligodendrocyte glycoprotein (MOG), glial fibrillary acidic protein (GFAP) are also described. Besides the known pathomechanisms with direct pathogenic effects of primary neuronal Abs and activation of innate (dendritic cells) and adaptive (B and T cells) immune systems, research findings suggest the involvement of glial cells including astrocytes, microglia, oligodendrocytes in the pathogenesis of Ab-associated AE, but only a limited number of studies is available. Neuropathologic findings showed reactive astrogliosis and microgliosis with microglial activation/proliferation, e.g., in anti-NMDAR and anti-LGI1 encephalitis. Direct effects of the GABA_AR and NMDAR Abs on astrocytic receptors are discussed. Because of the primary involvement of B and T cells in the pathogenesis of Ab-associated AE it can be assumed that astrocytic and microglial activation is largely a response to the primary changes, but additional direct effects of Abs on astrocytic receptors are possible. Further research in this field is required to explore the exact role of glial cells in Ab-associated AE.