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

Autoři: Sebastian Wawrocki aff001;  Michal Seweryn aff002;  Grzegorz Kielnierowski aff003;  Wieslawa Rudnicka aff001;  Marcin Wlodarczyk aff001;  Magdalena Druszczynska aff001
Působiště autorů: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, Poland aff001;  Center for Medical Genomics OMICRON, Jagiellonian University, Medical College, Cracow, Poland aff002;  Regional Specialized Hospital of Tuberculosis, Lung Diseases and Rehabilitation, Szpitalna 5, Tuszyn, Poland aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225556



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.

Klíčová slova:

Biomarkers – Bovine tuberculosis – Enzyme-linked immunoassays – Serum proteins – Tuberculosis – Tuberculosis diagnosis and management – Signaling complexes


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2019 Číslo 12