Yunxia Wan1, Xi Xhang1, John J Atherton2, Karam Kostner3, Goce Dimeski4, Chamindie Punyadeera5. 1. The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia. 2. Department of Cardiology, Royal Brisbane and Women's Hospital, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 3. Department of Cardiology, Mater Adult Hospital, Brisbane, Queensland, Australia. 4. School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Chemical Pathology Princess Alexandra Hospital, Brisbane, Queensland, Australia. 5. The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia. Electronic address: chamindie.punyadeera@qut.edu.au.
Abstract
BACKGROUND: We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies. METHODS: Plasma samples were collected from healthy controls (n=52) and HF patients (n=46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13-45, 13-76, 28-76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated. RESULTS: Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13-76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13-76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13-76 with NT-proBNP28-76 assays gave the best diagnostic assay performance. CONCLUSION: Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.
BACKGROUND: We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies. METHODS: Plasma samples were collected from healthy controls (n=52) and HF patients (n=46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13-45, 13-76, 28-76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated. RESULTS: Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13-76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13-76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13-76 with NT-proBNP28-76 assays gave the best diagnostic assay performance. CONCLUSION: Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.
Authors: Xi Zhang; Terry Walsh; John J Atherton; Karam Kostner; Benjamin Schulz; Chamindie Punyadeera Journal: Theranostics Date: 2017-09-26 Impact factor: 11.556