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:10.1371/journal.pone.0202191

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

Research output: Contribution to journal › Article › peer-review

15 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 language	English
Article number	e0202191
Journal	PLoS ONE
Volume	13
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0202191
State	Published - Sep 2018

Bibliographical note

Publisher Copyright:
© 2018 Huaman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

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

Funders	Funder number
CenterforAdvancingTranslationalSciences
Thisworkwassupportedinpartbythe UniversityofCincinnatiDepartmentofInternal Medicine
National Institutes of Health (NIH)
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	UM1AI069501
National Center for Advancing Translational Sciences (NCATS)	KL2 TR001426, UL1 TR000117
University of Cincinnati University Research Council

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General

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10.1371/journal.pone.0202191

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Huaman, M. A., Henson, D., Rondan, P. L., Ticona, E., Miranda, G., Kryscio, R. J., Mugruza, R., Aranda, E., Ticona, C., Abarca, S., Heredia, P., Aguirre, A., Sterling, T. R., Garvy, B. A., & Fichtenbaum, C. J. (2018). Latent tuberculosis infection is associated with increased unstimulated levels of interferon-gamma in Lima, Peru. PLoS ONE, 13(9), Article e0202191. https://doi.org/10.1371/journal.pone.0202191

@article{17373764203242049aa99c632057ea3d,

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

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{\textregistered} 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{\textendash}52.8 vs. 6.5 pg/mL, 4.5{\textendash}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{\textendash}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{\textendash}8.2). Conclusions LTBI was associated with higher unstimulated interferon-gamma levels. These data suggest ongoing immune activation in LTBI.",

author = "Huaman, \{Moises A.\} and David Henson and Rondan, \{Paola L.\} and Eduardo Ticona and Gustavo Miranda and Kryscio, \{Richard J.\} and Raquel Mugruza and Ernesto Aranda and Cesar Ticona and Susan Abarca and Paula Heredia and Andres Aguirre and Sterling, \{Timothy R.\} and Garvy, \{Beth A.\} and Fichtenbaum, \{Carl J.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Huaman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2018",

month = sep,

doi = "10.1371/journal.pone.0202191",

language = "English",

volume = "13",

number = "9",

}

Huaman, MA, Henson, D, Rondan, PL, Ticona, E, Miranda, G, Kryscio, RJ, Mugruza, R, Aranda, E, Ticona, C, Abarca, S, Heredia, P, Aguirre, A, Sterling, TR, Garvy, BA & Fichtenbaum, CJ 2018, 'Latent tuberculosis infection is associated with increased unstimulated levels of interferon-gamma in Lima, Peru', PLoS ONE, vol. 13, no. 9, e0202191. https://doi.org/10.1371/journal.pone.0202191

TY - JOUR

T1 - Latent tuberculosis infection is associated with increased unstimulated levels of interferon-gamma in Lima, Peru

AU - Huaman, Moises A.

AU - Henson, David

AU - Rondan, Paola L.

AU - Ticona, Eduardo

AU - Miranda, Gustavo

AU - Kryscio, Richard J.

AU - Mugruza, Raquel

AU - Aranda, Ernesto

AU - Ticona, Cesar

AU - Abarca, Susan

AU - Heredia, Paula

AU - Aguirre, Andres

AU - Sterling, Timothy R.

AU - Garvy, Beth A.

AU - Fichtenbaum, Carl J.

N1 - Publisher Copyright: © 2018 Huaman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/85053277854#tab=citedBy

U2 - 10.1371/journal.pone.0202191

DO - 10.1371/journal.pone.0202191

M3 - Article

C2 - 30212453

AN - SCOPUS:85053277854

SN - 1932-6203

VL - 13

JO - PLoS ONE

JF - PLoS ONE

IS - 9

M1 - e0202191

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

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