PLoS ONE (Jan 2018)

Latent tuberculosis infection is associated with increased unstimulated levels of interferon-gamma in Lima, Peru.

  • Moises A Huaman,
  • David Henson,
  • Paola L Rondan,
  • Eduardo Ticona,
  • Gustavo Miranda,
  • Richard J Kryscio,
  • Raquel Mugruza,
  • Ernesto Aranda,
  • Cesar Ticona,
  • Susan Abarca,
  • Paula Heredia,
  • Andres Aguirre,
  • Timothy R Sterling,
  • Beth A Garvy,
  • Carl J Fichtenbaum

DOI
https://doi.org/10.1371/journal.pone.0202191
Journal volume & issue
Vol. 13, no. 9
p. e0202191

Abstract

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BACKGROUND:We previously reported increased unstimulated blood levels of interferon-gamma in persons with latent tuberculosis infection (LTBI) in the United States, suggesting enhanced immune activation in LTBI. To investigate this further in a TB-endemic setting, we assessed interferon-gamma levels in persons with and without LTBI in Peru. METHODS:We analyzed data from patients with and without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were enrolled from two public hospital networks in Lima, Peru, and underwent LTBI testing using the QuantiFERON® TB Gold In-tube (QFT) assay. Participants with a positive QFT test were defined as having LTBI, whereas participants with a negative QFT test were defined as non-LTBI. Unstimulated interferon-gamma was quantified via enzyme-linked immunosorbent assay in the QFT nil-tube, which does not contain antigens. We compared unstimulated interferon-gamma levels between LTBI and non-LTBI groups using the Wilcoxon rank sum test. We used proportional odds modeling for multivariable analysis. RESULTS:Data from 214 participants were included in this analysis. Of those, 120 (56%) had LTBI. There were no significant differences in age, sex and comorbidities between LTBI and non-LTBI participants, except for recent AMI that was more frequent in LTBI. LTBI participants had higher unstimulated interferon-gamma levels compared to non-LTBI participants (median, interquartile range; 14 pg/mL, 6.5-52.8 vs. 6.5 pg/mL, 4.5-15; P<0.01). LTBI remained associated with higher unstimulated interferon-gamma levels after controlling for age, sex, recent AMI, history of hypertension, diabetes mellitus, dyslipidemia, end stage renal disease, malignancy, obesity, and tobacco use (adjusted odds ratio, 2.93; 95% confidence interval, 1.8-4.9). In a sensitivity analysis that excluded participants with AMI, the association between unstimulated interferon-gamma and LTBI remained present (adjusted odds ratio; 3.93; 95% confidence interval, 1.9-8.2). CONCLUSIONS:LTBI was associated with higher unstimulated interferon-gamma levels. These data suggest ongoing immune activation in LTBI.