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

Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Romulo Ticona Chavez, 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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere0202191
JournalPLoS ONE
Volume13
Issue number9
DOIs
StatePublished - Sep 2018
Externally publishedYes

Bibliographical note

Funding Information:
Funding:Thisworkwassupportedinpartbythe UniversityofCincinnatiDepartmentofInternal Medicine(JuniorFacultyPilotAward),theNational CenterforAdvancingTranslationalSciences(grant numbersUL1TR000117totheUniversityof KentuckyandKL2TR001426totheUniversityof

Funding Information:
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. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the institutions with which the authors are affiliated.

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