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. 2022 Aug;50(4):897-905.
doi: 10.1007/s15010-022-01760-8. Epub 2022 Feb 8.

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

Paulin N Essone #  1   2   3 , Bayode R Adegbite #  4   5   6 , Marien J M Mbadinga  4 , Armel V Mbouna  4 , Fabrice Lotola-Mougeni  4 , Ayodele Alabi  4   7 , Jean R Edoa  4   6 , Bertrand Lell  4   8 , Abraham S Alabi  4   5 , Ayola A Adegnika  4   5   7 , Michael Ramharter  4   9 , Joel F D Siawaya  10 , Martin P Grobusch  4   5   6 , Peter G Kremsner  4   5 , Selidji T Agnandji  11   12   13
Affiliations

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

Paulin N Essone et al. Infection. 2022 Aug.

Abstract

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.

Keywords: Biomarkers; Creatine kinase-MB; Diagnosis; Hepcidin; Tuberculosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Scatter-dot plots and ROC curves of analytes discriminating TB disease to alternative pulmonary diseases. Representative dot plots showing the levels of analytes in serum and ROC curves for accuracy in the diagnosis of TB disease. Error bars in the dot plots represent the median analyte levels
Fig. 2
Fig. 2
ROC curves analysis of the most discriminative two and tree markers models
See this image and copyright information in PMC

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