Advances in Potential Cerebrospinal Fluid Biomarkers for Autoimmune Encephalitis: A Review

Abstract

Autoimmune encephalitis (AE) is a severe inflammatory disease of the brain. Patients with AE demonstrate amnesia, seizures, and psychosis. Recent studies have identified numerous associated autoantibodies (e.g., against NMDA receptors (NMDARs), LGI1, etc.) involved in the pathogenesis of AE, and the levels of diagnosis and treatment are thus improved dramatically. However, there are drawbacks of clinical diagnosis and treatment based solely on antibody levels, and thus the application of additional biomarkers is urgently needed. Considering the important role of immune mechanisms in AE development, we summarize the relevant research progress in identifying cerebrospinal fluid (CSF) biomarkers with a focus on cytokines/chemokines, demyelination, and nerve damage.

Keywords: Autoimmune encephalitis (AE); biomarker; cerebrospinal fluid; cytokines/chemokines; demyelination; nerve damage.

Figure 1

The pathological effect caused by blood-brain barrier damage. The blood-brain barrier damage during AE progress is caused by Th17 cell activation, this leads to antibodies and lymphocytes entering the brain and cerebra-spinal fluid. Traditional methods for AE diagnosis are using CFS to detect relevant positive Ab, while novel approach to diagnose AE are using potential biomarkers, including cytokines/chemokines and molecules like MOG, AQP4 and S100 protein that expressed on nerve cells.

Figure 2

Associated cells involved in AE pathological processes. (A) Under the action of different cytokines, naive T cells differentiate into different Th cells. As a joint result of IL-6, STAT3, IL-17, TGF-β, naive T cells differentiate into Th 17 cells. The subsequent production of IL-17, IL-21, IL-22 by Th 17 cells triggers the immune response and impairs the blood brain barrier. In addition, IL-17A triggers a positive feedback loop of IL-6 signaling, leading to IL-17A/IL-6 co-activation. IL-12 activation can induce Th 1 cell differentiation. Furthermore, Th 1 cells secrete cytokines, such as TNF-α and IFN-γ, resulting in different outcomes. (B,C) As chemokines, CXCL13 and CXCL10 induce directional chemotaxis of B cells and T cells, respectively, towards the target sites. (D) The production of YK-40 by microglia contributes to the early diagnosis.