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Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon

BACKGROUND: The present study aimed to evaluate the diagnostic utility of creatine kinase-MB (CK-MB), hepcidin (HEPC), phospholipase A2 group IIA (PLa2G2A), and myosin-binding protein C (MYBPC1) for tuberculosis (TB). These four biomarkers are differentially regulated between quiescent Mycobacterium...

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Autores principales: Essone, Paulin N., Adegbite, Bayode R., Mbadinga, Marien J. M., Mbouna, Armel V., Lotola-Mougeni, Fabrice, Alabi, Ayodele, Edoa, Jean R., Lell, Bertrand, Alabi, Abraham S., Adegnika, Ayola A., Ramharter, Michael, Siawaya, Joel F. D., Grobusch, Martin P., Kremsner, Peter G., Agnandji, Selidji T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338130/
https://www.ncbi.nlm.nih.gov/pubmed/35133607
http://dx.doi.org/10.1007/s15010-022-01760-8
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author Essone, Paulin N.
Adegbite, Bayode R.
Mbadinga, Marien J. M.
Mbouna, Armel V.
Lotola-Mougeni, Fabrice
Alabi, Ayodele
Edoa, Jean R.
Lell, Bertrand
Alabi, Abraham S.
Adegnika, Ayola A.
Ramharter, Michael
Siawaya, Joel F. D.
Grobusch, Martin P.
Kremsner, Peter G.
Agnandji, Selidji T.
author_facet Essone, Paulin N.
Adegbite, Bayode R.
Mbadinga, Marien J. M.
Mbouna, Armel V.
Lotola-Mougeni, Fabrice
Alabi, Ayodele
Edoa, Jean R.
Lell, Bertrand
Alabi, Abraham S.
Adegnika, Ayola A.
Ramharter, Michael
Siawaya, Joel F. D.
Grobusch, Martin P.
Kremsner, Peter G.
Agnandji, Selidji T.
author_sort Essone, Paulin N.
collection PubMed
description BACKGROUND: The present study aimed to evaluate the diagnostic utility of creatine kinase-MB (CK-MB), hepcidin (HEPC), phospholipase A2 group IIA (PLa2G2A), and myosin-binding protein C (MYBPC1) for tuberculosis (TB). These four biomarkers are differentially regulated between quiescent Mycobacterium tuberculosis (Mtb) infected individuals (non-progressors to TB disease) and Mtb-infected TB disease progressors 6 months before the onset of symptoms. METHODS: We enrolled samples from patients experiencing moderate-to-severe pulmonary infections diseases including 23 TB cases confirmed by smear microscopy and culture, and 34 TB-negative cases. For each participant, the serum levels of the four biomarkers were measured using ELISA. RESULTS: The levels of CK-MB and HEPC were significantly reduced in patients with active TB disease. CK-MB median level was 2045 pg/ml (1455–4000 pg/ml) in active TB cases and 3245 pg/ml (1645–4000 pg/ml) in non-TB pulmonary diseases. Using the receiver operating characteristic curve (ROC) analysis, HEPC and CK-MB had the Area Under the Curve (AUC) of 79% (95% CI 67–91%) and 81% (95% CI 69–93%), respectively. Both markers correlated with TB diagnosis as a single marker. PLa2G2A and MYBPC1 with AUCs of 48% (95% CI 36–65%) and 62% (95% CI 48–76%) did not performed well as single biomarkers. The three markers’model (CK-MB-HEPC-PLa2G2A) had the highest diagnostic accuracy at 82% (95% CI 56–82%) after cross-validation. CONCLUSION: CK-MB and HEPC levels were statistically different between confirmed TB cases and non-TB cases. This study yields promising results for the rapid diagnosis of TB disease using a single marker or three biomarkers model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s15010-022-01760-8.
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spelling pubmed-93381302022-07-31 Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon Essone, Paulin N. Adegbite, Bayode R. Mbadinga, Marien J. M. Mbouna, Armel V. Lotola-Mougeni, Fabrice Alabi, Ayodele Edoa, Jean R. Lell, Bertrand Alabi, Abraham S. Adegnika, Ayola A. Ramharter, Michael Siawaya, Joel F. D. Grobusch, Martin P. Kremsner, Peter G. Agnandji, Selidji T. Infection Original Paper BACKGROUND: The present study aimed to evaluate the diagnostic utility of creatine kinase-MB (CK-MB), hepcidin (HEPC), phospholipase A2 group IIA (PLa2G2A), and myosin-binding protein C (MYBPC1) for tuberculosis (TB). These four biomarkers are differentially regulated between quiescent Mycobacterium tuberculosis (Mtb) infected individuals (non-progressors to TB disease) and Mtb-infected TB disease progressors 6 months before the onset of symptoms. METHODS: We enrolled samples from patients experiencing moderate-to-severe pulmonary infections diseases including 23 TB cases confirmed by smear microscopy and culture, and 34 TB-negative cases. For each participant, the serum levels of the four biomarkers were measured using ELISA. RESULTS: The levels of CK-MB and HEPC were significantly reduced in patients with active TB disease. CK-MB median level was 2045 pg/ml (1455–4000 pg/ml) in active TB cases and 3245 pg/ml (1645–4000 pg/ml) in non-TB pulmonary diseases. Using the receiver operating characteristic curve (ROC) analysis, HEPC and CK-MB had the Area Under the Curve (AUC) of 79% (95% CI 67–91%) and 81% (95% CI 69–93%), respectively. Both markers correlated with TB diagnosis as a single marker. PLa2G2A and MYBPC1 with AUCs of 48% (95% CI 36–65%) and 62% (95% CI 48–76%) did not performed well as single biomarkers. The three markers’model (CK-MB-HEPC-PLa2G2A) had the highest diagnostic accuracy at 82% (95% CI 56–82%) after cross-validation. CONCLUSION: CK-MB and HEPC levels were statistically different between confirmed TB cases and non-TB cases. This study yields promising results for the rapid diagnosis of TB disease using a single marker or three biomarkers model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s15010-022-01760-8. Springer Berlin Heidelberg 2022-02-08 2022 /pmc/articles/PMC9338130/ /pubmed/35133607 http://dx.doi.org/10.1007/s15010-022-01760-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Essone, Paulin N.
Adegbite, Bayode R.
Mbadinga, Marien J. M.
Mbouna, Armel V.
Lotola-Mougeni, Fabrice
Alabi, Ayodele
Edoa, Jean R.
Lell, Bertrand
Alabi, Abraham S.
Adegnika, Ayola A.
Ramharter, Michael
Siawaya, Joel F. D.
Grobusch, Martin P.
Kremsner, Peter G.
Agnandji, Selidji T.
Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title_full Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title_fullStr Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title_full_unstemmed Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title_short Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambaréné, Gabon
title_sort creatine kinase-(mb) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in lambaréné, gabon
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338130/
https://www.ncbi.nlm.nih.gov/pubmed/35133607
http://dx.doi.org/10.1007/s15010-022-01760-8
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