Open AccessIL-18/IL-37/IP-10 signalling complex as a potential biomarker for discriminating active and latent TB
Author(s) -
Sebastian Wawrocki,
Michał Seweryn,
Grzegorz Kielnierowski,
Wiesława Rudnicka,
Marcin Włodarczyk,
Magdalena Druszczyńska
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0225556
Subject(s) - latent tuberculosis , mycobacterium tuberculosis , biomarker , tuberculosis , immunology , medicine , interleukin 10 , antigen , cytokine , biology , biochemistry , pathology
Background 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. Methods 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. Results 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. Conclusions 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.