Cerebrospinal fluid soluble CD27 is a sensitive biomarker of inflammation in autoimmune encephalitis

J Neurol Sci. 2024 Nov 15:466:123226. doi: 10.1016/j.jns.2024.123226. Epub 2024 Sep 10.

Abstract

Background: Autoimmune encephalitis (AE) comprises a group of rare, severe neuroinflammatory conditions. Current biomarkers of neuroinflammation are often normal in AE which therefore can be difficult to rule out in patients with seizures, cognitive and/or neuropsychiatric symptoms. Cerebrospinal fluid (CSF) soluble CD27 (sCD27) and soluble B-cell maturation antigen (sBCMA) have high sensitivity for neuroinflammation in other neuroinflammatory conditions. In this exploratory study we investigate the potential of sCD27 and sBCMA in CSF as biomarkers of neuroinflammation in AE.

Methods: Concentrations of sCD27 and sBCMA were measured in CSF from 40 AE patients (20 patients were untreated (12 with anti-N-Methyl-d-Aspartate receptor antibodies (NMDA) and 8 with anti-Leucine-rich Glioma-Inactivated 1 antibodies (LGI1)), and 37 symptomatic controls (SCs).

Results: CSF concentrations of sCD27 were increased in untreated NMDA AE patients (median 1571 pg/ml; p < 0.001) and untreated LGI1 AE patients (median 551 pg/ml; p < 0.05) compared to SCs (median 250 pg/ml). CSF sBCMA was increased in untreated NMDA AE patients (median 832 pg/ml) compared to SCs (median 429 pg/ml). CSF sCD27 and sBCMA correlated with the CSF cell count. Receiver operating characteristic curve analysis of untreated AE patients versus SCs showed an area under the curve of 0.97 for sCD27 and 0.76 for sBCMA.

Conclusion: CSF sCD27 is a suitable biomarker of neuroinflammation in AE with an ability to discriminate patients with NMDA AE and LGI1 AE from symptomatic controls. CSF sCD27 may be suited for ruling out AE and other neuroinflammatory conditions in the early phase of the diagnostic work-up.

Keywords: Autoimmune encephalitis; Biomarkers; Cerebrospinal fluid; Neuroinflammation; Soluble CD27.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / cerebrospinal fluid
  • Biomarkers* / cerebrospinal fluid
  • Encephalitis* / cerebrospinal fluid
  • Encephalitis* / diagnosis
  • Female
  • Hashimoto Disease / cerebrospinal fluid
  • Hashimoto Disease / diagnosis
  • Humans
  • Inflammation / cerebrospinal fluid
  • Inflammation / diagnosis
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Tumor Necrosis Factor Receptor Superfamily, Member 7*
  • Young Adult

Substances

  • Biomarkers
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Autoantibodies
  • LGI1 protein, human
  • Intracellular Signaling Peptides and Proteins

Supplementary concepts

  • Hashimoto's encephalitis