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A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

Togun, Toyin, Hoggart, Clive, Agbla, Schadrac, Gomez, Marie, Egere, Uzochukwu, Sillah, Abdou, Saidy, Binta, Mendy, Francis, Pai, Madhukar and Kampmann, Beate (2020) 'A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children'. EBioMedicine, Vol 58, Issue 102909.

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Abstract

Background
Our study aimed to identify a host cytokine biosignature that could distinguish childhood tuberculosis (TB) from other respiratory diseases (OD).

Methods
Cytokine responses in prospectively recruited children with symptoms suggestive of TB were measured in whole blood assay supernatants, harvested after overnight incubation, using a Luminex platform. We used logistic regression models with Least Absolute Shrinkage and Selection Operator (LASSO) penalty to identify the optimal biosignature associated with confirmed TB disease in the training set. We subsequently assessed its performance in the test set.

Findings
Of the 431 children included in the study, 44 had bacteriologically confirmed TB, 60 had clinically diagnosed TB while 327 had OD. All children were HIV-negative. Application of LASSO regression models to the training set (n = 260) resulted in the combination of IL-1ra, IL-7 and IP-10 from unstimulated samples as the optimally discriminant cytokine biosignature associated with bacteriologically confirmed TB. In the test set (n = 171), this biosignature distinguished children diagnosed with TB disease, irrespective of microbiological confirmation, from OD with area under the receiver operator characteristic curve (AUC) of 0•74 (95% CI: 0•67, 0•81), and demonstrated sensitivity and specificity of 72•2% (95% CI: 60•4, 82•1%) and 75•0% (95% CI: 64•9, 83•4%) respectively, with its performance independent of their age group and their age- and sex-adjusted nutritional status.

Interpretation
This novel biosignature of childhood TB derived from unstimulated supernatants is promising. Independent validation with further optimisation will improve its performance and translational potential.

Funding
Steinberg Fellowship (McGill University); Grand Challenges Canada; MRC Program Grant.

Item Type: Article
Subjects: WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department: Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.ebiom.2020.102909
Depositing User: Elly Wallis
Date Deposited: 10 Aug 2020 13:08
Last Modified: 10 Aug 2020 13:08
URI: https://archive.lstmed.ac.uk/id/eprint/15243

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