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Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study

Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 month...

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Autores principales: Lee, Meng-Rui, Tsai, Chia-Jung, Wang, Wei-Jie, Chuang, Tzu-Yi, Yang, Chih-Mann, Chang, Lih-Yu, Lin, Ching-Kai, Wang, Jann-Yuan, Shu, Chin-Chong, Lee, Li-Na, Yu, Chong-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616826/
https://www.ncbi.nlm.nih.gov/pubmed/26426648
http://dx.doi.org/10.1097/MD.0000000000001628
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author Lee, Meng-Rui
Tsai, Chia-Jung
Wang, Wei-Jie
Chuang, Tzu-Yi
Yang, Chih-Mann
Chang, Lih-Yu
Lin, Ching-Kai
Wang, Jann-Yuan
Shu, Chin-Chong
Lee, Li-Na
Yu, Chong-Jen
author_facet Lee, Meng-Rui
Tsai, Chia-Jung
Wang, Wei-Jie
Chuang, Tzu-Yi
Yang, Chih-Mann
Chang, Lih-Yu
Lin, Ching-Kai
Wang, Jann-Yuan
Shu, Chin-Chong
Lee, Li-Na
Yu, Chong-Jen
author_sort Lee, Meng-Rui
collection PubMed
description Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment. Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624–0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512–0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (<440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status. Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence.
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spelling pubmed-46168262015-10-27 Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study Lee, Meng-Rui Tsai, Chia-Jung Wang, Wei-Jie Chuang, Tzu-Yi Yang, Chih-Mann Chang, Lih-Yu Lin, Ching-Kai Wang, Jann-Yuan Shu, Chin-Chong Lee, Li-Na Yu, Chong-Jen Medicine (Baltimore) 4900 Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment. Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624–0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512–0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (<440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status. Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence. Wolters Kluwer Health 2015-10-02 /pmc/articles/PMC4616826/ /pubmed/26426648 http://dx.doi.org/10.1097/MD.0000000000001628 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle 4900
Lee, Meng-Rui
Tsai, Chia-Jung
Wang, Wei-Jie
Chuang, Tzu-Yi
Yang, Chih-Mann
Chang, Lih-Yu
Lin, Ching-Kai
Wang, Jann-Yuan
Shu, Chin-Chong
Lee, Li-Na
Yu, Chong-Jen
Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title_full Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title_fullStr Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title_full_unstemmed Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title_short Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study
title_sort plasma biomarkers can predict treatment response in tuberculosis patients: a prospective observational study
topic 4900
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616826/
https://www.ncbi.nlm.nih.gov/pubmed/26426648
http://dx.doi.org/10.1097/MD.0000000000001628
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