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Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.

ABSTRACT: Granulysin (GNLY) is produced by human lymphocyte subpopulations and exhibits antimicrobial activity against Mycobacterium tuberculosis. We examined the association between GNLY levels in blood and latent tuberculosis (TB) infection.Latency of TB infection among Vietnamese healthcare workers was estimated using interferon-gamma release assays (IGRA), and serum GNLY concentrations were measured using enzyme-linked immunosorbent assays. The levels of GNLY expression in whole blood and the presence of GNLY alleles with the exon-4 polymorphism rs11127 were also determined using PCR-based methods.Among 109 study participants, 41 (37.6 %) were IGRA positive and had significantly lower serum GNLY concentrations compared with IGRA-negative participants (adjusted mean, 95 % confidence interval; 2.03, 1.72-2.44 vs. 2.48, 2.10-2.92 ng/ml, P = 0.0127; analysis of covariance). Serum GNLY concentrations and TB antigen-stimulated interferon-gamma values were weakly inversely correlated (r = -0.20, P = 0.0333). Serum GNLY concentrations varied with GNLY genotypes even after adjustment for gender and age (adjusted P = 0.0015) and were moderately correlated with GNLY expression in blood cells (r = 0.40, P < 0.0001). In subsequent analyses, low serum GNLY concentrations were significantly associated with IGRA status (adjusted odds ratio and 95 % confidence interval, 0.55 and 0.31-0.98, respectively), although GNLY genotype and mRNA levels were not.Decreased GNLY, presumably at the protein level, is linked to the immunological condition of latent TB infection.

SUBMITTER: Thuong PH

PROVIDER: S-EPMC5070182 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.

Thuong Pham Huu PH Tam Do Bang DB Sakurada Shinsaku S Hang Nguyen Thi Le NT Hijikata Minako M Hong Le Thi LT Ngoc Phan Thi Minh PT Anh Pham Thu PT Cuong Vu Cao VC Matsushita Ikumi I Lien Luu Thi LT Keicho Naoto N

BMC infectious diseases 20161018 1

<h4>Background</h4>Granulysin (GNLY) is produced by human lymphocyte subpopulations and exhibits antimicrobial activity against Mycobacterium tuberculosis. We examined the association between GNLY levels in blood and latent tuberculosis (TB) infection.<h4>Methods</h4>Latency of TB infection among Vietnamese healthcare workers was estimated using interferon-gamma release assays (IGRA), and serum GNLY concentrations were measured using enzyme-linked immunosorbent assays. The levels of GNLY express ...[more]

PMID: 27756230

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Project description:Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI) is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI diagnosis in various patient populations using Bayesian latent class modelling.Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85%) and 52% (50-53%), respectively. The specificity of QFT-GIT was 97% (96-97%) in non-BCG-vaccinated and 93% (92-94%) in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100%) and 79% (76-82%), respectively. T-SPOT.TB has comparable specificity (97% for both tests) and better sensitivity (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT-GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG-vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in children.This study is the first to assess the utility of TST and IGRAs for LTBI diagnosis in different population groups using all available data with Bayesian latent class modelling. Our results challenge the current beliefs about the performance of LTBI screening tests, and have important implications for LTBI screening policy and practice. We estimated that the performance of IGRAs is not as reliable as previously measured in the general population. However, IGRAs are not or minimally affected by BCG and should be the preferred tests in this setting. Adoption of IGRAs in settings where BCG is widely administered will allow for a more accurate identification and treatment of LTBI.

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Dataset Information

Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.

Publications

Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.

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