Delta-like 1 protein, vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis

Biomark Med. 2018 Jul;12(7):707-716. doi: 10.2217/bmm-2017-0373. Epub 2018 Jun 1.

Abstract

Aim: Tuberculosis meningitis (TBM) diagnosis is difficult, new biomarkers are needed. We evaluated the diagnostic utility of delta-like 1 protein (DLL1), vitamin D binding protein (VDBP) and fetuin.

Methods: Biomarker concentrations were measured by ELISA in cryopreserved cerebrospinal fluid from 139 HIV-infected Ugandans with suspected meningitis. TBM was diagnosed by GeneXpert MTB/Rif or culture. Cohort diagnoses included TBM (n = 22), cryptococcal (n = 71), or aseptic meningitis (n = 16) and no meningitis (n = 30).

Results: DLL1 (cut-off value 1150 pg/ml) provided 32% sensitivity and 98% specificity. Adding fetuin, cryptococcal antigen and IFN-γ resulted in sensitivities of 36, 63 and 76% with specificities of 98, 90 and 92%, respectively. VDBP (cut-off value 2.0 μg/ml) provided 81% sensitivity and 68% specificity while fetuin (cut-off value 2 μg/ml) provided a sensitivity of 86% and specificity of 68%.

Conclusion: CSF DLL1, VDBP and fetuin exhibited fair diagnostic performance for TBM diagnosis.

Keywords: Mycobacterium tuberculosis; TB meningitis; biomarkers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid
  • Calcium-Binding Proteins
  • Female
  • Fetuins / cerebrospinal fluid*
  • Humans
  • Intercellular Signaling Peptides and Proteins / cerebrospinal fluid*
  • Male
  • Membrane Proteins / cerebrospinal fluid*
  • Middle Aged
  • Mycobacterium tuberculosis / physiology*
  • ROC Curve
  • Tuberculosis, Meningeal / cerebrospinal fluid*
  • Tuberculosis, Meningeal / diagnosis*
  • Vitamin D-Binding Protein / cerebrospinal fluid*

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Fetuins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Vitamin D-Binding Protein