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.
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.
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).
LTBI was associated with higher unstimulated interferon-gamma levels. These data suggest ongoing immune activation in LTBI.
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This work was supported in part by the University of Cincinnati Department of Internal Medicine (Junior Faculty Pilot Award), the National Center for Advancing Translational Sciences (grant numbers UL1 TR000117 to the University of Kentucky and KL2 TR001426 to the University of Cincinnati), and the National Institute of Allergy and Infectious Diseases (grant number UM1 AI069501; CJF), both at the National Institutes of Health.
All relevant data are within the paper and its Supporting Information files.
S1 File. Dataset. https://doi.org/10.1371/journal.pone.0202191.s001 (XLSX)
Huaman, Moises A.; Henson, David; Rondan, Paola L.; Ticona, Eduardo; Miranda, Gustavo; Kryscio, Richard J.; Mugruza, Raquel; Aranda, Ernesto; Ticona, Cesar; Abarca, Susan; Heredia, Paula; Aguirre, Andres; Sterling, Timothy R.; Garvy, Beth A.; and Fichtenbaum, Carl J., "Latent Tuberculosis Infection is Associated with Increased Unstimulated Levels of Interferon-Gamma in Lima, Peru" (2018). Internal Medicine Faculty Publications. 164.