Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis

Abstract

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).

Recent Advances in Diagnosis and Management of Female Genital Tuberculosis

“…In vitro fertilization and embryo transfer and surrogacy have a role in selected cases. Newer molecule tests like genomics and nucleus receptors are being developed for early diagnosis of TB including FGTB [ 50 ]. Novel biotechniques, nanoparticles and stem cell transplantation are being developed for regeneration of endometrium (in Asher man’s syndrome), fallopian tubes (fallopian tubes blockage and damage) and for ovaries (damaged ovaries).…”

Incidence rate of active tuberculosis in solid organ transplant recipients: Data from a nationwide population cohort in a high‐endemic country

“…Multifunctional CD4+ T lymphocytes producing multiple cytokines along with IL‐2 can protect against TB reactivation 52–54 . In addition, patients with active TB have increased levels of IL‐2R, and depict of IL‐2‐inducible T‐cell kinase, highly expressed in Th1 and Th17 cells, have been shown to induce the vulnerability of TB in murine studies 55,56 . Therefore, basiliximab might be associated with a lower risk of TB, especially compared to ATG.…”

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…Wang et al (2018) identified a six-cytokine biosignature (including IFNγ, IL-10, IL-1Ra, IP-10, VEGF, and IL-12p70) to discriminate between aTB and LTBI, resulting in a sensitivity of 88.2% and a specificity of 92.1% in a biomarker validation cohort (n = 216) and a sensitivity of 85.7% and a specificity of 91.3% in a prospectively recruited clinical validation cohort (n = 194), respectively. Coincidentally, Korma et al (2020) evaluated the sensitivity, specificity, and accuracy of the combination of seven cytokines (IFN-γ, IP-10, IL-2R, C-X-C Motif Chemokine Ligand 9 (CXCL-9), IL-10, IL-4, and TNF-α) based on gene expression in differentiating between aTB and LTBI. They demonstrated that the combination of IL-10, IP-10, and IL-4 could differentiate pulmonary patients with TB from latent patients with TB with a sensitivity and specificity of 77.1% and 88.1%, respectively (Korma et al, 2020).…”

“…Coincidentally, Korma et al (2020) evaluated the sensitivity, specificity, and accuracy of the combination of seven cytokines (IFN-γ, IP-10, IL-2R, C-X-C Motif Chemokine Ligand 9 (CXCL-9), IL-10, IL-4, and TNF-α) based on gene expression in differentiating between aTB and LTBI. They demonstrated that the combination of IL-10, IP-10, and IL-4 could differentiate pulmonary patients with TB from latent patients with TB with a sensitivity and specificity of 77.1% and 88.1%, respectively (Korma et al, 2020). Luo et al (2019) identified potential biomarkers from 38 plasma cytokines to discriminate among the different stages of M. tuberculosis infection in its study participants, who were composed of 78 patients with aTB, 73 patients with LTBI, and 76 HCs.…”