Low CSF CD4/CD8+ T-cell proportions are associated with blood-CSF barrier dysfunction in limbic encephalitis

Epilepsy Behav. 2020 Jan;102:106682. doi: 10.1016/j.yebeh.2019.106682. Epub 2019 Dec 14.


Purpose: Investigating immune cells in autoimmune limbic encephalitis (LE) will contribute to our understanding of its pathophysiology and may help to develop appropriate therapies. The aim of the present study was to analyze immune cells to reveal underlying immune signatures in patients with temporal lobe epilepsy (TLE) with LE.

Methods: We investigated 68 patients with TLE with LE compared with 7 control patients with TLE with no signs of LE screened from 154 patients with suspected LE. From the patients with TLE-LE, we differentiated early seizure onset (<20 years, n = 9) and late seizure onset group (≥20 years, n = 59) of patients. Patients underwent neuropsychological assessment, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and peripheral blood (PB) and cerebrospinal fluid (CSF) analysis including flow cytometry.

Results: We identified a higher CD4/8+ T-cell ratio in the PB in all patients with TLE-LE and in patients with late-onset TLE-LE each compared with controls (Kruskal-Wallis one-way ANOVA (analysis of variance) with Dunn's test, p < 0.05). Moreover, a lower CD4/CD8+ T-cell ratio is detected in all patients with TLE-LE with blood-CSF barrier dysfunction, unlike in those with none (Kruskal-Wallis one-way ANOVA with Dunn's test, p < 0.05).

Conclusions: These findings suggest that the proportion of CD4+ and CD8+ T-cells in the CSF of patients with LE associated with blood-CSF barrier dysfunction plays a potential role in CNS (central nervous system) inflammation in these patients. Thus, flow cytometry as a methodology reveals novel insights into LE's genesis and symptomatology. The CD4/8+ T-cell ratio in PB as a biomarker for LE requires further investigation.

Keywords: Autoimmunity; B-cells; Blood–CSF barrier; Limbic encephalitis; T-cells; Temporal lobe epilepsy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Autoimmune Diseases / cerebrospinal fluid*
  • Autoimmune Diseases / diagnostic imaging*
  • Autoimmune Diseases / physiopathology
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / physiopathology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Electroencephalography / methods
  • Epilepsy, Temporal Lobe / cerebrospinal fluid*
  • Epilepsy, Temporal Lobe / diagnostic imaging*
  • Epilepsy, Temporal Lobe / physiopathology
  • Female
  • Humans
  • Limbic Encephalitis / cerebrospinal fluid*
  • Limbic Encephalitis / diagnostic imaging*
  • Limbic Encephalitis / physiopathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Young Adult


  • Biomarkers

Supplementary concepts

  • Autoimmune limbic encephalitis