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Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care co...

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Autores principales: Morris, Thomas C., Hoggart, Clive J., Chegou, Novel N., Kidd, Martin, Oni, Tolu, Goliath, Rene, Wilkinson, Katalin A., Dockrell, Hazel M., Sichali, Lifted, Banda, Louis, Crampin, Amelia C., French, Neil, Walzl, Gerhard, Levin, Michael, Wilkinson, Robert J., Hamilton, Melissa S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947659/
https://www.ncbi.nlm.nih.gov/pubmed/33717190
http://dx.doi.org/10.3389/fimmu.2021.639174
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author Morris, Thomas C.
Hoggart, Clive J.
Chegou, Novel N.
Kidd, Martin
Oni, Tolu
Goliath, Rene
Wilkinson, Katalin A.
Dockrell, Hazel M.
Sichali, Lifted
Banda, Louis
Crampin, Amelia C.
French, Neil
Walzl, Gerhard
Levin, Michael
Wilkinson, Robert J.
Hamilton, Melissa S.
author_facet Morris, Thomas C.
Hoggart, Clive J.
Chegou, Novel N.
Kidd, Martin
Oni, Tolu
Goliath, Rene
Wilkinson, Katalin A.
Dockrell, Hazel M.
Sichali, Lifted
Banda, Louis
Crampin, Amelia C.
French, Neil
Walzl, Gerhard
Levin, Michael
Wilkinson, Robert J.
Hamilton, Melissa S.
author_sort Morris, Thomas C.
collection PubMed
description Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86–95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80–98%) and 71% (95% CI 56–84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64–76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures.
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spelling pubmed-79476592021-03-12 Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa Morris, Thomas C. Hoggart, Clive J. Chegou, Novel N. Kidd, Martin Oni, Tolu Goliath, Rene Wilkinson, Katalin A. Dockrell, Hazel M. Sichali, Lifted Banda, Louis Crampin, Amelia C. French, Neil Walzl, Gerhard Levin, Michael Wilkinson, Robert J. Hamilton, Melissa S. Front Immunol Immunology Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86–95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80–98%) and 71% (95% CI 56–84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64–76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947659/ /pubmed/33717190 http://dx.doi.org/10.3389/fimmu.2021.639174 Text en Copyright © 2021 Morris, Hoggart, Chegou, Kidd, Oni, Goliath, Wilkinson, Dockrell, Sichali, Banda, Crampin, French, Walzl, Levin, Wilkinson and Hamilton. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Morris, Thomas C.
Hoggart, Clive J.
Chegou, Novel N.
Kidd, Martin
Oni, Tolu
Goliath, Rene
Wilkinson, Katalin A.
Dockrell, Hazel M.
Sichali, Lifted
Banda, Louis
Crampin, Amelia C.
French, Neil
Walzl, Gerhard
Levin, Michael
Wilkinson, Robert J.
Hamilton, Melissa S.
Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title_full Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title_fullStr Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title_full_unstemmed Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title_short Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa
title_sort evaluation of host serum protein biomarkers of tuberculosis in sub-saharan africa
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947659/
https://www.ncbi.nlm.nih.gov/pubmed/33717190
http://dx.doi.org/10.3389/fimmu.2021.639174
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