α1-acid glycoprotein and α1-antitrypsin as early markers of treatment response in patients receiving the intensive phase of tuberculosis therapy

Almeida, Maria Luíza Dória; Barbieri, Marco Antônio; Gurgel, Ricardo Queiróz; Abdurrahman, Saddiq T.; Baba, Uthman Alhaji; Shenkin, Alan; Silva, Angela Maria; Souza, Luiz de; Cuevas, Luís E.

doi:10.1016/j.trstmh.2008.11.024

Cited by 17 publications

(14 citation statements)

References 18 publications

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“…However, we know that a proportion of LTBI at some point reactivate and develop active disease, and this may be preceded by a “fight” between host and microorganism leading to inflammatory responses that could have long term impact on the infected person. The acute phase reactant alpha-1-acid glycoprotein (AGP) has previously been associated with active TB [7], [8] and it might be a marker of inflammation in regards to LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting in a TB high endemic country.…”

Section: Introductionmentioning

confidence: 99%

The Prevalence of Latent Mycobacterium tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey among Urban Adults in Mwanza, Tanzania

Jensen

Faurholt‐Jepsen

et al. 2013

PLoS ONE

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IntroductionOne third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls.MethodsThe study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI.Results245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10B 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test.ConclusionLTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies.

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Section: Introductionmentioning

confidence: 99%

The Prevalence of Latent Mycobacterium tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey among Urban Adults in Mwanza, Tanzania

Jensen

Faurholt‐Jepsen

et al. 2013

PLoS ONE

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“…The literature also supports the idea that a slower decline in these biomarkers over the course of treatment correlates with poorer treatment response [18,41]. Many have reported in small studies that CRP, sIL-2Rα, sTNF-R1, sTNF-r2, and neopterin were higher at baseline or failed to decline as rapidly in slower treatment responders or treatment failures[8,9,12,17,18,28,41]. Here, we have replicated the findings of Siawaya and colleagues in observing a treatment-related decline in all analytes except granzyme B, but no difference in these analytes between fast and slow treatment responders (as defined by 8 week culture status) in univariate analyses.…”

Section: Resultsmentioning

confidence: 68%

“…Multiple studies have reported that levels of these markers either correlate with TB infection, disease extent and severity, or decline over the course of intensive therapy[7,10,13-15,24,27,39,40]. The literature also supports the idea that a slower decline in these biomarkers over the course of treatment correlates with poorer treatment response [18,41]. Many have reported in small studies that CRP, sIL-2Rα, sTNF-R1, sTNF-r2, and neopterin were higher at baseline or failed to decline as rapidly in slower treatment responders or treatment failures[8,9,12,17,18,28,41].…”

Section: Resultsmentioning

confidence: 96%

Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis

Jayakumar¹,

Vittinghoff²,

Segal³

et al. 2015

Tuberculosis

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Rationale Biomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda. Methods We consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age. Results All but one analyte decreased from baseline to week 8 (all p<0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8 C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer-Lemeshow P>0.2). Conclusion Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.

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“…Recent studies have identified blood transcriptional signatures that correlate with disease severity and reversion in response to treatment [45] or patients who relapse rather than achieve lasting cures [46]. Other studies [47–49] have evaluated the serum host biomarkers reflecting treatment responses at earlier time points or in relation to sputum culture conversion. One important advantage of our findings, is that circulating BK and DABK levels represent the host's response to pathogen–associated molecular patterns and may offer a rational route forward in the prediction of real-time treatment outcomes at both early and late treatment stages and allow individualization of treatment regimens, dosing, and treatment duration.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series

Qian

Nguyen

et al. 2016

Tuberculosis

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Background There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg9-bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. Methods Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. Results Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. Conclusions Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We will further exploit these host-response signatures in the future as biomarkers in combination with other clinical and microbiologic tools which may improve treatment efficacy and facilitate the development of host-directed therapy.

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α1-acid glycoprotein and α1-antitrypsin as early markers of treatment response in patients receiving the intensive phase of tuberculosis therapy

Cited by 17 publications

References 18 publications

The Prevalence of Latent Mycobacterium tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey among Urban Adults in Mwanza, Tanzania

The Prevalence of Latent Mycobacterium tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey among Urban Adults in Mwanza, Tanzania

Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series

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