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Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis.
Garay-Baquero, Diana J; White, Cory H; Walker, Naomi F; Tebruegge, Marc; Schiff, Hannah F; Ugarte-Gil, Cesar; Morris-Jones, Stephen; Marshall, Ben G; Manousopoulou, Antigoni; Adamson, John; Vallejo, Andres F; Bielecka, Magdalena K; Wilkinson, Robert J; Tezera, Liku B; Woelk, Christopher H; Garbis, Spiros D; Elkington, Paul.
Afiliación
  • Garay-Baquero DJ; School of Clinical and Experimental Sciences, Faculty of Medicine, and.
  • White CH; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
  • Walker NF; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, California, USA.
  • Tebruegge M; School of Clinical and Experimental Sciences, Faculty of Medicine, and.
  • Schiff HF; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
  • Ugarte-Gil C; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
  • Morris-Jones S; Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
  • Marshall BG; TB Centre and Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Manousopoulou A; Department of Paediatric Infectious Diseases & Immunology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Adamson J; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
  • Vallejo AF; Department of Paediatrics, University of Melbourne, Parkville, Australia.
  • Bielecka MK; School of Clinical and Experimental Sciences, Faculty of Medicine, and.
  • Wilkinson RJ; TB Centre and Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Tezera LB; Instituto de Medicina Tropical Alexander von Humboldt, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
  • Woelk CH; Department of Microbiology, University College London Hospitals NHS Trust, London, United Kingdom.
  • Garbis SD; Division of Infection and Immunity, University College London, London, United Kingdom.
  • Elkington P; School of Clinical and Experimental Sciences, Faculty of Medicine, and.
JCI Insight ; 5(18)2020 09 17.
Article en En | MEDLINE | ID: mdl-32780727
BACKGROUNDTuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma.METHODSWe applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203).RESULTSWe generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low-molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81).CONCLUSIONWe report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test.FUNDINGColciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Biomarcadores / Proteoma / Mycobacterium tuberculosis Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: Africa / America do sul / Peru Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Biomarcadores / Proteoma / Mycobacterium tuberculosis Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: Africa / America do sul / Peru Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos