Garlant, Harriet N;
Ellappan, Kalaiarasan;
Hewitt, Matthew;
Perumal, Prem;
Pekeleke, Simon;
Wand, Nadina;
Southern, Jo;
... Kempsell, Karen E; + view all
(2022)
Evaluation of Host Protein Biomarkers by ELISA From Whole Lysed Peripheral Blood for Development of Diagnostic Tests for Active Tuberculosis.
Frontiers in Immunology
, 13
, Article 854327. 10.3389/fimmu.2022.854327.
Preview |
Text
Abubakar_fimmu-13-854327.pdf - Published Version Download (4MB) | Preview |
Abstract
Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations.
| Type: | Article |
|---|---|
| Title: | Evaluation of Host Protein Biomarkers by ELISA From Whole Lysed Peripheral Blood for Development of Diagnostic Tests for Active Tuberculosis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2022.854327 |
| Publisher version: | https://doi.org/10.3389/fimmu.2022.854327 |
| Language: | English |
| Additional information: | Copyright © 2022 Garlant, Ellappan, Hewitt, Perumal, Pekeleke, Wand, Southern, Kumar, Belgode, Abubakar, Sinha, Vasan, Joseph and Kempsell. 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. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, biomarker, protein, ELISA, tuberculosis, diagnostic, assay, diagnosis, TB, DISEASE, AUTOPHAGY, FAMILY, ASSAYS, TLR3 |
| UCL classification: | UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10152476 |
Archive Staff Only
 |
View Item |
