Urine NMR-based TB metabolic fingerprinting for the diagnosis of TB in children
Comella-del-Barrio, Patricia; Izquierdo-Garcia, José Luis; Gautier, Jacqueline; Doresca, Mariette Jean Coute; Campos-Olivas, Ramón; Santiveri, Clara M.; Muriel-Moreno, Beatriz; Prat-Aymerich, Cristina; Abellana, Rosa; Pérez-Porcuna, Tomas M.; Cuevas, Luis E.; Ruiz-Cabello, Jesús; Domínguez, José
(2021) Scientific Reports, volume 11, issue 1
(Article)
Abstract
Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with
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different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.
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Keywords: General
ISSN: 2045-2322
Publisher: Nature Publishing Group
Note: Funding Information: The authors would like to thank Dr Margareth Narcisse, Mr Movil Junior Wilfrid, Mr Louis Yves and Ms Achil Nancy, and the laboratory technicians from the Paediatric Hospital Saint Damien of the Nos Petits Frères et Sœurs Foundation, Port-au-Prince for their collaboration and valuable assistance and care during recruitment and sampling. We also thank Federico Casanova (Magritek GmbH, Aachen, Germany) for providing the Spinsolve 60 Ultra Spectrometer to acquire the LF urine spectra and for technical support. Finally, we thank Dr Beatriz Sallés Mingels and Dr Lydia Canales Aliaga from the radiology service of the Primary Care Centre of Manso, and Dr Jaume Ollé Goig from the ACTMON Association for his support to the TB unit of the Saint Damien Hospital, for his indirect but positive influence on this project. This research was supported by grants from: (i) the Isolana Foundation; (ii) the Maria Francesca Roviralta Foundation (iii) the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC-AEI) (SAF2017-84494-C2-1-R); (vi) the Instituto de Salud Carlos III (PI13/01546, PI16/01912, and DTS18/0092), integrated in the Plan Nacional de I+D+I, and cofounded by the ISCIII Subdirec-ción General de Evaluación and the European Reginal Development Fund (ERDF); (v) the Spanish Ministry of Science and Innovation (PID2019-10656RJ-I00); (vi) the Sociedad Española de Neumología y Cirugía Torácica (project 052/2011; SEPAR; Barcelona, Spain); (vii) the Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE: 02730-16 and 3307-17); (viii) the Comunidad de Madrid (B2017/BMD3875); (ix) the Gobierno Vasco, Dpto. Industria, Innovación, Comercio y Turismo, under the ELKARTEK programme (No. KK-2019/ bmG19); and (x) the European Respiratory Society—ERS Short-Term Research Fellowship (October 2018) for C. Prat-Aymerich STRTF201810-00467; and (xi) the European Union’s Horizon 2020 Research and Innovation Programme, under the Marie Skłodowska-Curie grant agreement no. 823854 (INNOVA4TB). JRC received grants from the BBVA Foundation (Ayudas a Equipos de Investigación Científica de Biomedicina 2018) and from La Caixa Foundation (Health Research Call 2020 / HR20-00075). CIC biomaGUNE is supported by the Maria de Maeztu Units of Excellence Programme from the Spanish State Research Agency (Grant No. MDM-2017-0720). The funders were not involved at any stage from study design to submission of the manuscript for publication. Publisher Copyright: © 2021, The Author(s).
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