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

Abstract

Se reportó previamente el incremento sin estimulación de niveles de interferón-gama en sangre, en personas con infección latente de tuberculosis (LTBI), en Estados Unidos, sugiriendo activación inmune mejorada en LTBI. Para investigar esto en un entorno endémico de tuberculosis, se evaluó los niveles de interferón gama in personas con y sin infección latente de tuberculosis en Perú. Se analizó la información de pacientes con y sin un reciente infarto agudo de miocardio tipo 1, seleccionados del Hospital Nacional Dos de Mayo y del Hospital Nacional Edgardo Rebagliati Martins in Lima, Perú, entre julio del 2015 y marzo de 2017. Se les hizo un examen de infección latente de tuberculosis usando el ensayo QuantiFERON® TB Gold In-tube (QFT), los pacientes con QFT positivo se definieron que tenían infección latente de tuberculosis. El interferón-gama no estimulado fue cuantificado vía prueba de ELISA (enzyme-linked immunosorbent assay). Se comparó los niveles de interferón-gama no estimulado entre los grupos con y sin infección latente de tuberculosis.

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 nonLTBI 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.