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

Abstract

BackgroundGranulysin (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.MethodsLatency 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.ResultsAmong 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.ConclusionsDecreased GNLY, presumably at the protein level, is linked to the immunological condition of latent TB infection.

Serum Granulysin in Differentiation of Stevens-Johnson Syndrome/toxic Epidermal Necrolysis and Erythema Multiforme

“…By using the sandwich ELISA method, a study in Japan shows the mean level of serum granulysin among healthy individuals is 3.7 ng/ml, and it also demonstrates a positive correlation between serum granulysin levels and age, but no significant difference in serum granulysin levels between genders [33]. Furthermore, a study among health staffs from tuberculosis hospitals in Hanoi, Vietnam, also shows lower levels of serum granulysin as compared with those of the present study [35]. This may be due to the difference in study populations, age, and immunological conditions.…”

“…Nevertheless, our results may imply the use of serum granulysin as a biomarker for distinguishing between EM and SJS/TEN. In fact, serum granulysin levels can be affected by some factors such as infection [33], [34], [35], sepsis [36], cancers [34], [37], age [33], and immunological condition [35], hence, it was a large range among our SJS/ TEN patients. However, systemic corticosteroid treatment before hospitalization did not affect serum granulysin levels in patients with SJS/TEN.…”

Latent tuberculosis infection in healthcare workers in low- and middle-income countries: an updated systematic review

“…https://doi.org/10.1183/13993003.01789-2018 9 TUBERCULOSIS | L. APRIANI ET AL. [47,62,68,76,93], male sex [37, 48,52,76], household contact [10,76,96], BCG scar/vaccination [37,47], level of education [48,56], body mass index (BMI) [56,90], granulysin concentration [90] and diabetes mellitus [10]. In HCSs, older age and khat consumption were the only significant non-occupational factors [34].…”

Biomarcadores da tuberculose: uma revisão da literatura.

“…Considerando os trabalhadores positivos para IGRA como LTBI, os autores observam a correlação negativa entre o IFN-γ e a GNL nesse estágio da infecção (THUONG et al, 2016). Os mecanismos para essa apresentação da molécula são bastante vagos, mas os autores propõem a hipótese de que o sequestro e acúmulo de células produtoras da GNL ao redor de granulomas possa ser uma das explicações, bem como o consumo da molécula pela imunidade efetora que estaria agindo no combate ao Mtb.…”