Search

Background: Accurate diagnosis of tuberculosis (TB) in children continues to be challenging, primarily due to the low bacterial load characteristic of the disease and the obstacles in collecting sputum samples. Furthermore, detecting cases of latent Mycobacterium tuberculosis (M.tb) infection (LTBI) that have a high risk of progressing to active TB disease remains a significant diagnostic hurdle., Objective: The study explored the utility of interferon-gamma (IFN-γ) inducible protein 10 (IP-10) for diagnosing latent and active M.tb infections among children vaccinated with the Bacille Calmette-Guerin (BCG) vaccine. The research specifically assessed IP-10 levels in serum, urine, and QuantiFERON-TB Gold Plus (QFT) cultures stimulated with M.tb antigens to determine if IP-10 could be a useful diagnostic marker for pediatric tuberculosis, either alongside or as an alternative to IFN-γ., Results: Both urine and QFT cultures stimulated with M.tb antigens showed significantly higher IP-10 levels in individuals with active TB or latent TB infection (LTBI) when compared to those uninfected by M.tb but with nonmycobacterial pneumonia (NMP) and healthy controls (HC). Similarly, IFN-γ levels in M.tb-stimulated QFT cultures were significantly higher in the TB and LTBI groups compared to the NMP and HC groups. Notably, the study found a significant difference in IFN-γ levels between the TB and LTBI groups in the QFT cultures, a distinction not observed for IP-10 concentrations. Serum levels of IP-10 and IFN-γ did not significantly vary across the study cohorts., Conclusions: IP-10 might be a viable alternative biomarker to IFN-γ for identifying M.tb infection in BCG-vaccinated children, although it cannot distinguish between latent and active TB cases. This highlights the potential of IP-10 in improving TB diagnosis among children, addressing the challenges posed by the paucibacillary nature of pediatric TB, but also underscores the need for further research to refine diagnostic approaches for distinguishing between latent and active TB infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Druszczynska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist.

The skin tuberculin test (TST), an example of a delayed-type hypersensitivity (DTH) reaction, is based on measuring the extent of skin induration to mycobacterial tuberculin (PPD). Little is known about the genetic basis of TST reactivity, widely used for diagnosing TB infection. The study investigated the relationship of the single base change polymorphic variants in CD14 gene (CD14(-159C/T)) with the development of DTH to PPD in BCG-vaccinated Polish Caucasian individuals. We found persistent lack of TST reactivity in about 40% of healthy subjects despite receiving more than one dose of BCG. The TST size was negatively correlated with the number of BCG inoculations. The distribution of C/T genotype was significantly more frequent among TST-negative compared with TST-positive individuals. The concentration of serum sCD14 was positively associated with mCD14 expression, but not with the TST status or CD14(-159C/T) polymorphism. A significant increase in mCD14 expression and serum sCD14 levels was found in TB group. We hypothesize that CD14(-159C/T) polymorphic variants might be one of genetic components in the response to attenuated M. bovis BCG bacilli.