Chapter 10 - Autoimmune Astrocytopathy

Abstract

Astrocytes constitute the most abundant type of glial cells in the central nervous system (CNS) and display significant heterogeneity. Astrocytes actively engage in various metabolic processes and are active contributors to immune responses within the CNS, with either beneficial or detrimental outcomes. The dynamic response of astrocytes to external signals leads to alterations in morphology, molecular expression, and function. In addition, autonomous cell-driven changes in innate properties may contribute to various autoimmune and neurodegenerative diseases.

The development of neuromyelitis optical spectrum disorder (NMOSD) is determined by pathogenic antibodies targeting the water channel aquaporin-4 (AQP4) located in astrocyte end feet. AQP4-IgG facilitates the differential diagnosis of NMOSD. Similarly, a newly identified autoantibody against GFAP serves as a biomarker for a relapsing autoimmune form of meningoencephalomyelitis, responsive to steroids and often associated with tumors. In Rasmussen’s encephalitis, CD8+ T lymphocytes induce astrocyte loss in affected areas, disrupting normal neuronal function. Additionally, astrocytes mediate multiple mechanisms involved in the genesis and progression of multiple sclerosis (MS) and remyelination processes. Finally, reactive astrocytes play a crucial role in various CNS infections, both during acute phases and in the long term, influencing the development of post-infectious sequelae. These observations underscore the active participation of astrocytes in both pathological and repair mechanisms observed in CNS immune-mediated diseases. Characterizing the cellular and molecular mechanisms underlying astrocyte pathophysiology represents a new frontier to identify novel therapeutic strategies for CNS pathologies.