Search for biomarkers of neurosarcoidosis by proteomic analysis of cerebrospinal fluid

Ann Biol Clin (Paris). 2017 Aug 1;75(4):393-402. doi: 10.1684/abc.2017.1260.


Sarcoidosis is a systemic granulomatous disease, which mostly affects lung. Central nervous system can be affected causing a neurosarcoidosis in 5 to 15% of all sarcoidosis patients. The definitive diagnosis is established on histological examination of brain granulomas. Angiotensin converting enzyme is currently the most relevant biomarker to confirm a probable diagnosis; however, it lacks sensitivity and specificity. We aim to find novel biomarkers of neurosarcoidosis in cerebrospinal fluid (CSF) by proteomic analysis, combining two-dimension electrophoresis (2-DE) and mass spectrometry. We performed CSF proteomic profile of both patients (group S) and control subjects (group H). The statistical analysis of 2-D gels highlighted 42 spots significantly different between the two groups. Twenty-five spots were subjected to tryptic digestion; the peptides were analyzed by MALDI-TOF and MALDI-TOF-TOF, giving rise to 10 identifications. Among the identified proteins, low-molecular-mass-kininogen and vitamin-D-binding-protein were increased, while transthyretin was decreased. These proteins have probably an intrathecal source and could be interesting candidates. This study led to the identification of several proteins which can be used for the diagnosis and/or monitoring of neurosarcoidosis. These putative biomarkers have to be confirmed on a larger cohort and assessed for their sensitivity and specificity.

Keywords: biomarkers; cerebrospinal fluid; mass spectrometry; neurosarcoidosis; two-dimensional electrophoresis.

MeSH terms

  • Biomarkers / cerebrospinal fluid*
  • Case-Control Studies
  • Central Nervous System Diseases / cerebrospinal fluid*
  • Central Nervous System Diseases / diagnosis*
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • Peptidyl-Dipeptidase A / analysis
  • Peptidyl-Dipeptidase A / cerebrospinal fluid
  • Proteomics / methods*
  • Sarcoidosis / cerebrospinal fluid*
  • Sarcoidosis / diagnosis*
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Biomarkers
  • ACE protein, human
  • Peptidyl-Dipeptidase A

Supplementary concepts

  • Neurosarcoidosis