The Immunopathogenesis of Autoimmune Encephalitis-Related Psychosis, A Comprehensive Review of Humoral and Cellular Mechanisms

Abstract

Autoimmune encephalitis has reshaped the understanding of neuropsychiatric disorders by highlighting the role of autoantibodies in psychosis symptoms, which often mimic primary psychosis conditions. This review synthesizes recent research on autoimmune encephalitis-related psychosis, broadening the focus from humoral immunity to T cell autoimmunity and the communication between the peripheral and central nervous systems. We discuss the identification of neuronal antigen targets, particularly the N-methyl-D-aspartate receptor (NMDAR), and their involvement in disease pathogenesis. Current treatments, such as plasma exchange and intravenous immunoglobulin, primarily target the pathogenicity of autoantibodies. However, emerging evidence suggests a crucial role for T cells, glia cell, and B cell in the immunopathogenesis of autoimmune encephalitis-related psychosis diseases. Autoimmune factors, including T and B cells, can either infiltrate the brain from the periphery or propagate via interacting with other cells, like glia, within the brain itself. This review advocates for a comprehensive approach to studying and treating these conditions, integrating both humoral and cellular mechanisms.

Keywords

Autoimmunity / Encephalitis / Psychiatric / Psychosis / NMDAR

Author Contributions

Writing-Original Draft Preparation, L.H.; Writing-Review & Editing, V.P., T.N.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Funding

This work was supported by the Wellcome Trust (226779/Z/22/Z) and by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2222), the UK Medical Research Council (CC2222), and the Wellcome Trust (CC2222).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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