The cerebrospinal fluid CD4/CD8 ratio and interleukin-6 and -10 levels in neurosarcoidosis: a multicenter, pragmatic, comparative study

Eur J Neurol. 2019 Oct;26(10):1274-1280. doi: 10.1111/ene.13975. Epub 2019 Jun 24.

Abstract

Background and purpose: Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL-10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients.

Methods: A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations.

Results: Forty-three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL-6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL-6 level was higher in patients with active neurosarcoidosis than in non-active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL-6 concentration >50 pg/ml was associated with a higher risk of relapse or progression-free survival (hazard ratio 3.60; 95% confidence interval 1.78-23.14). A refractory neurosarcoidosis patient was treated with an anti-IL-6 monoclonal antibody that produced a complete neurological response.

Conclusions: The CSF CD4/CD8 ratio and IL-6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL-6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL-10 levels may be elevated in neurosarcoidosis.

Keywords: central nervous system; cerebrospinal fluid; cytokine; interleukin; sarcoidosis; tocilizumab.

Publication types

  • Comparative Study
  • Multicenter Study
  • Pragmatic Clinical Trial

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid
  • CD4-CD8 Ratio*
  • Central Nervous System Diseases / cerebrospinal fluid*
  • Central Nervous System Diseases / immunology
  • Cerebrospinal Fluid / cytology*
  • Female
  • Humans
  • Inflammation / cerebrospinal fluid
  • Interleukin-10 / cerebrospinal fluid*
  • Interleukin-6 / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid
  • Progression-Free Survival
  • Recurrence
  • Retrospective Studies
  • Sarcoidosis / cerebrospinal fluid*
  • Sarcoidosis / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-10

Supplementary concepts

  • Neurosarcoidosis