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

Author:

Essone Paulin N.ORCID,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.

Abstract

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.

Funder

European and Developing Countries Clinical Trials Partnership

Eberhard Karls Universität Tübingen

Publisher

Springer Science and Business Media LLC

Subject

Infectious Diseases,Microbiology (medical),General Medicine

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