Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children.

Magdalena Druszczynska,Michal Seweryn,Wieslawa Rudnicka,Sebastian Wawrocki,Anna Pankowska,Magdalena Kowalewska-Pietrzak

doi:10.3390/pathogens10050517

Magdalena Druszczynska, Michal Seweryn + Show 4 more

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https://doi.org/10.3390/pathogens10050517

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Journal: Pathogens	Publication Date: Apr 24, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: University of Łódź

Abstract

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

Highlights

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a global health emergency with 10 million new cases and 1.5 million deaths annually
In the 5-fold cross-validation analysis between the HC versus latent M. tb infection (LTBI) groups, we identified the panel of proteins (IL6, APRIL/TNFSF13, sCD30/TNFRSF8, gp130/sIL-6β, IL-2, sIL-6Rα, IL-8, IL-29/IFNλ1, IL-35, matrix metalloproteinases (MMPs)-2, MMP-3, OPN, PTX-3, sTNF-R2, TWEAK/TNFSF12), while between the HC versus TB groups, proteins (APRIL/TNFSF13, sCD30/TNFRSF8, chitinase 3-like 1, sIL-6Rα, IL-8, IL-11, IL-12(p70), IL-19, IL-28A/IFN-λ2, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, OPN, PTX-3, TWEAK/TNFSF12) with the best discriminating potential (Table 4)
In addressing the need for better diagnostic tests allowing the differentiation of different stages of M.tb infection in children, the main aim of the study was to select biomarkers of anti-TB protective immunity versus TB disease in children among 53 biological molecules— Th17-related cytokines and inflammatory mediators, whose role in M.tb infections has already been suggested

Summary

Introduction

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a global health emergency with 10 million new cases and 1.5 million deaths annually. None of the currently available microbiological, serologic, or molecular tests designed for the diagnosis of active TB are good enough for clinical use in children. In low TB incidence countries, the diagnosis of pediatric TB is based on non-specific clinical symptoms, the presence of suggestive abnormal radiological features, a positive tuberculin skin test (TST) result, and the history of M.tb exposure [1]. These criteria have a limited application in TB endemic regions, because most individuals become TST-positive during childhood or adolescence. The implementation of chemoprophylaxis to a child with active TB is a serious error, which leads to failure of the treatment and an increased risk of the emergence of drug-resistant strains [1]

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