IL-6 release of Rv0183 antigen-stimulated whole blood is a potential biomarker for active tuberculosis patients

J Infect. 2018 Apr;76(4):376-382. doi: 10.1016/j.jinf.2017.11.004. Epub 2017 Nov 24.

Abstract

Objective: New tests for diagnosing active tuberculosis (aTB) are urgently needed, and TB antigen-specific cell-mediated immunity can be expected to develop new testing methods of aTB.

Materials and methods: Rv0183 protein, the only monoglyceride lipase identified in mycobacteria, was used to stimulate freshly heparin-treated whole blood. The Rv0183-specific cytokines/chemokines response associated with aTB was screened firstly with 4 aTB patients and 4 LTBIs, and further evaluated in 192 suspected aTB patients and 372 healthy individuals.

Results: Out of 71 cytokines/chemokines, the response of IL-6 against Rv0183 protein was found to be associated with aTB. The Rv0183-specific IL-6 response was significantly higher in aTB patients (n = 128) than in those with non-TB lung disease (n = 64) and in healthy individuals (n = 327) (p < 0.0001), and not affected by latent TB infection. In IGRA+ suspected active TB patients, the sensitivity, specificity, PPV and NPV of IL-6 response (with cutoff of 235.2 pg/ml) were 85.7%, 100%, 100% and 51.5% for diagnosing aTB, respectively. While in IGRA- ones, they were 87.5%, 80.5%, 60.9% and 95.0% with 174.2 pg/ml IL-6 response as cutoff, respectively.

Conclusions: These results clearly show that the Rv0183 antigen-specific IL-6 response has the potential to be used as an immune-diagnosis test for active TB in clinical practice.

Keywords: Active TB patients; IFN-γ release assay; IL-6; Rv0183.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / pharmacology*
  • Biomarkers / blood
  • Cytokines / analysis
  • Cytokines / immunology
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunity, Cellular
  • Immunologic Tests / methods*
  • Interferon-gamma Release Tests
  • Interleukin-6 / immunology*
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mycobacterium tuberculosis
  • Sensitivity and Specificity
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology*

Substances

  • Antigens, Bacterial
  • Biomarkers
  • Cytokines
  • IL6 protein, human
  • Interleukin-6