IL-18/IL-37/IP-10 signalling complex as a potential biomarker for discriminating active and latent TB.

Sebastian Wawrocki,Grzegorz Kielnierowski,Wieslawa Rudnicka,Marcin Wlodarczyk,Magdalena Druszczynska,Michal Seweryn

doi:10.1371/journal.pone.0225556

Sebastian Wawrocki, Grzegorz Kielnierowski + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0225556

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Journal: PloS one	Publication Date: Dec 10, 2019
Citations: 22	License type: CC BY 4.0

Affiliation: University of Łódź, Jagiellonian University

Abstract

Currently, there are serious limitations in the direct diagnosis of active tuberculosis (ATB). We evaluated the levels of the IL-18/IL-37/IP-10 signalling complex proteins in Mycobacterium tuberculosis (M.tb)-specific antigen-stimulated QuantiFERON® Gold In-Tube (QFT) cultures and in serum samples from ATB patients, healthy individuals with latent M.tb infection (LTBI) and healthy controls (HC) to examine whether combined analyses of these proteins were useful in the differentiation of M.tb states. The concentrations of IL-18, IL-18BP, IFN-γ, IL-37 and IP-10 in the serum and QFT supernatants were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. Free IL-18 levels were calculated using the law of mass action. Increased concentrations of total and free IL-18, IL-18BP, IFN-γ and IP-10 in the sera of ATB patients were detected. These increases were not counterbalanced by the overproduction of IL-37. Complex co-expression of serum IL-18BP and IL-37, IP-10 and IFN-γ was identified as the highest discriminative biomarker set for the diagnosis of ATB. Our results suggest that the IL-18 signalling complex might be exploited by M. tuberculosis to expand the clinical manifestations of pulmonary TB. Therefore, direct analysis of the serum components of the IL-18/IL-37 signalling complex and IP-10 may be applicable in designing novel diagnostic tests for ATB.

Highlights

Tuberculosis (TB) affects approximately 10 million people causing 2 million deaths annually [1]
We evaluated the levels of the IL-18/IL-37/IP-10 signalling complex proteins in Mycobacterium tuberculosis (M.tb)-specific antigen-stimulated QuantiFERON® Gold In-Tube (QFT) cultures and in serum samples from active tuberculosis (ATB) patients, healthy individuals with latent M.tb infection (LTBI) and healthy controls (HC) to examine whether combined analyses of these proteins were useful in the differentiation of M.tb states
To the total IL-18 level, the serum concentration of IL-18 binding protein (IL-18BP) was significantly higher in ATB patients (Me 43.5 (IQR 31.7, 60.4) ng/ml, culture-positive (Me 44.9 (IQR 32.5, 59.3) ng/ml, culture-negative (Me 43.4 (IQR 27.8, 77.2) ng/ml) than in latent tuberculosis infection (LTBI) (Me 28.8 (IQR 21.1, 42.8) ng/ml; p

Summary

Introduction

Tuberculosis (TB) affects approximately 10 million people causing 2 million deaths annually [1]. The remaining 90–95% of individuals mount an immune response and develop latent tuberculosis infection (LTBI) [2]. The immune status of the host’s macrophages and T cells and the activation of cytokines, primarily IFN-γ, control the granuloma structure and M.tb replication in asymptomatic LTBI. Interferongamma release assays (IGRAs) are used to diagnose LTBI These tests measure the release of IFN-γ in response to M.tb-specific antigens in whole blood cultures. We evaluated the levels of the IL-18/IL-37/IP-10 signalling complex proteins in Mycobacterium tuberculosis (M.tb)-specific antigen-stimulated QuantiFERON® Gold In-Tube (QFT) cultures and in serum samples from ATB patients, healthy individuals with latent M.tb infection (LTBI) and healthy controls (HC) to examine whether combined analyses of these proteins were useful in the differentiation of M.tb states

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