IL-18/IL-37/IP-10 signalling complex as a potential biomarker for discriminating active and latent TB.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
Chemokine CXCL10
/ blood
Cohort Studies
Diagnosis, Differential
Female
Humans
Intercellular Signaling Peptides and Proteins
/ blood
Interferon-gamma
/ blood
Interleukin-1
/ blood
Interleukin-18
/ blood
Latent Tuberculosis
/ blood
Male
Middle Aged
Poland
Tuberculosis, Pulmonary
/ blood
Young Adult
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
29
05
2019
accepted:
06
11
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
9
4
2020
Statut:
epublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 31821340
doi: 10.1371/journal.pone.0225556
pii: PONE-D-19-15207
pmc: PMC6903724
doi:
Substances chimiques
Biomarkers
0
CXCL10 protein, human
0
Chemokine CXCL10
0
IFNG protein, human
0
IL18 protein, human
0
IL37 protein, human
0
Intercellular Signaling Peptides and Proteins
0
Interleukin-1
0
Interleukin-18
0
interleukin-18 binding protein
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0225556Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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