Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

PLoS One. 2020 Jul 20;15(7):e0235859. doi: 10.1371/journal.pone.0235859. eCollection 2020.

Abstract

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Chemokine CX3CL1 / analysis
  • Chemokine CX3CL1 / blood*
  • Chemokine CXCL10 / analysis
  • Chemokine CXCL10 / blood*
  • Female
  • Humans
  • Interleukins / analysis
  • Interleukins / blood*
  • Latent Tuberculosis / blood*
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / metabolism
  • Male
  • Middle Aged
  • Saliva / chemistry
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / metabolism
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Biomarkers
  • Chemokine CX3CL1
  • Chemokine CXCL10
  • Interleukins
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by the EU Horizon2020 Eliciting Mucosal Immunity in Tuberculosis (EMI-TB) project [Grant Number 643558] (https://ec.europa.eu/programmes/horizon2020/en) and the Xunta de Galicia “Grupo de Referencia Competitiva 2016” [Grant number ED431C 2016/041] (https://www.edu.xunta.gal/portal/es/node/26897). O.E. acknowledges a fellowship from the Spanish Ministry of Education [Grant number FPU 13/03026] (http://www.educacionyfp.gob.es/servicios-al-ciudadano/catalogo/general/99/998758/ficha/998758-2019.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.