Cytokine/chemokine levels in the CSF and serum of anti-NMDAR encephalitis: A systematic review and meta-analysis

Front Immunol. 2023 Jan 23:13:1064007. doi: 10.3389/fimmu.2022.1064007. eCollection 2022.

Abstract

Objectives: To summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells in the pathogenic mechanism.

Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched for various articles that assessed the concentrations of cytokines/chemokines in the unstimulated cerebrospinal fluid (CSF) or serum of patients with NMDAR-E in this systematic review and meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by Stata17.0.

Results: A total of 19 articles were included in the systematic review from 260 candidate papers, and cytokine/chemokine levels reported in the CSF/serum were examined in each article. This meta-analysis included 17 eligible studies comprising 579 patients with NMDAR-E, 367 patients with noninflammatory neurological disorders, and 42 healthy controls from China, Spain, South Korea, Australia, Czechia, and Sweden. The results indicated that the levels of different cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, IL-13, IL-1β, IL-12, and IL-17 and chemokine C-X-C motif ligand (CXCL)10 in the CSF were significantly higher in NMDAR-E patients with a large effect size. In addition, B cell activating factor (BAFF), CXCL13, and interferon (IFN)-γ levels in the CSF were higher in NMDAR-E patients with a middle effect size. In contrast, levels of IL-2 and IL-4 in the CSF and CXCL13 and BAFF in the serum did not show a significant difference between cases and controls.

Conclusions: These analyses showed that the central immune response in NMDAR-E is a process that involves multiple immune cell interactions mediated by cytokines/chemokines, and T cells play an important role in the pathogenesis of immunity.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022342485).

Keywords: NMDAR encephalitis; T cell; chemokine; cytokine; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / blood
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / cerebrospinal fluid
  • Chemokines* / blood
  • Chemokines* / cerebrospinal fluid
  • Cytokines* / blood
  • Cytokines* / cerebrospinal fluid
  • Humans
  • Interleukin-12
  • Interleukin-6
  • Tumor Necrosis Factor-alpha

Substances

  • Chemokines
  • Cytokines
  • Interleukin-12
  • Interleukin-6
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the Natural Science Foundation of Sichuan Province(Grant Number 2022NSFSC1504).