Elevated Spontaneous Interferon-γ Secretion in Human Immunodeficiency Virus-Infected Persons

Sparks, Rachel; Koelle, David M.; Stern, Joshua; Dhanireddy, Shireesha

doi:10.1093/ofid/ofx055

Cited by 13 publications

(9 citation statements)

References 15 publications

(14 reference statements)

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“…These results are consistent with our previous report of elevated IFN-γ levels in a U.S. population with LTBI [ 15 ]. Our results are also consistent with a recent study conducted in Seattle, Washington that found higher geometric mean of QFT nil-tube IFN-γ values in QFT positive vs. QFT negative individuals with and without HIV infection, although these differences were not adjusted by comorbidities [ 22 ].…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, in a sensitivity analysis that excluded participants with AMI, the association between IFN-γ and LTBI remained present. Unstimulated IFN-γ levels seemed overall higher than levels reported in prior studies [ 15 , 22 ], likely because our population was older, primarily inpatient, comorbidities were frequent, and socioeconomic conditions were different across studies. Therefore, these results should not be generalized to the overall population.…”

Section: Discussioncontrasting

confidence: 63%

“…Although the source of IFN-γ in QFT nil tubes is unknown, it may indicate spontaneous IFN-γ secretion by activated lymphocytes and/or other blood cells, thus reflecting a degree of ongoing immune activation in LTBI patients. Supporting this idea, IFN-γ levels in QFT nil tubes are elevated in individuals with other conditions characterized by chronic immune activation such as HIV infection, even when HIV viral loads are < 200 copies/mL [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our analysis had limitations. Prior studies showed that unstimulated IFN-γ levels were associated with total peripheral blood lymphocyte counts [ 15 , 22 ]. We did not measure lymphocyte counts and therefore could not account for this potential confounder.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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BackgroundWe 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.MethodsWe 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.ResultsData 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).ConclusionsLTBI was associated with higher unstimulated interferon-gamma levels. These data suggest ongoing immune activation in LTBI.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…IFN-γ is a cytokine secreted by activated T cells and NK cells with a wide range of immune response functions, such as macrophage activation, antiviral and antibacterial immunity mediation, and several other important immunoregulatory functions [44]. IFN-γ has been observed in higher concentrations within PWH compared to HD [45], and PWH with high levels of circulating IFN-γ exhibited a lower CD4 + T cell count recovery after 4 years of being on cART [46]. Additionally, IFN-γ trended positively with age among HD.…”

Section: Discussionmentioning

confidence: 99%

Multiplex analysis of cytokines and chemokines in persons aging with or without HIV

Kroll

Woolley

Terry

et al. 2023

Preprint

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People with HIV (PWH) on combined antiretroviral therapy (cART) are living longer lives due to modern cART advances and increased routine medical care. The full landscape of aging with HIV is unclear; given that HIV emerged relatively recently in human history and initially had a high mortality rate, there has not been a substantially aged population to evaluate. In the present study, we set out to perform high throughput plasma analyte profiling by multiplex analysis, focusing on various T helper (Th)-related cytokines, chemokines, and pro- and anti-inflammatory cytokines. The primary goals being to provide reference ranges of these analytes for aging PWH cohorts, as well as testing the utility of high throughput multiplex plasma assays. The cohort used in this study was comprised of age-matched healthy donors (aged 32.6-73.5), PWH on cART (aged 26.7-60.2), and viremic PWH (aged 27.5-59.4). The patients in each group were then stratified across the age span to examine age-related impacts of these plasma biomarkers. Our results largely indicate feasibility of plasma analyte monitoring by multiplex and demonstrate a high degree of person-to-person variability regardless of age and HIV status. Nonetheless, we find multiple associations with age, duration of known infection, and viral load, all of which appear to be driven by either prolonged HIV disease progression or long-term use of cART.

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In silico designing of novel epitope-based peptide vaccines against HIV-1

Heidarnejad,

Namvar,

Sadat

et al. 2024

Biotechnol Lett

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Elevated Spontaneous Interferon-γ Secretion in Human Immunodeficiency Virus-Infected Persons

Cited by 13 publications

References 15 publications

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

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

Multiplex analysis of cytokines and chemokines in persons aging with or without HIV

In silico designing of novel epitope-based peptide vaccines against HIV-1

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