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Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease

Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; c...

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Autores principales: Arshad, Haroon, Siokis, Anastasios, Franke, Raimo, Habib, Aamna, Alfonso, Juan Carlos López, Poliakova, Yuliya, Lücke, Eva, Michaelis, Katina, Brönstrup, Mark, Meyer-Hermann, Michael, Bilitewski, Ursula, Vila, Jordi, Abel, Laurent, Illig, Thomas, Schreiber, Jens, Pessler, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330610/
https://www.ncbi.nlm.nih.gov/pubmed/35892580
http://dx.doi.org/10.3390/cells11152283
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author Arshad, Haroon
Siokis, Anastasios
Franke, Raimo
Habib, Aamna
Alfonso, Juan Carlos López
Poliakova, Yuliya
Lücke, Eva
Michaelis, Katina
Brönstrup, Mark
Meyer-Hermann, Michael
Bilitewski, Ursula
Vila, Jordi
Abel, Laurent
Illig, Thomas
Schreiber, Jens
Pessler, Frank
author_facet Arshad, Haroon
Siokis, Anastasios
Franke, Raimo
Habib, Aamna
Alfonso, Juan Carlos López
Poliakova, Yuliya
Lücke, Eva
Michaelis, Katina
Brönstrup, Mark
Meyer-Hermann, Michael
Bilitewski, Ursula
Vila, Jordi
Abel, Laurent
Illig, Thomas
Schreiber, Jens
Pessler, Frank
author_sort Arshad, Haroon
collection PubMed
description Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD.
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spelling pubmed-93306102022-07-29 Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease Arshad, Haroon Siokis, Anastasios Franke, Raimo Habib, Aamna Alfonso, Juan Carlos López Poliakova, Yuliya Lücke, Eva Michaelis, Katina Brönstrup, Mark Meyer-Hermann, Michael Bilitewski, Ursula Vila, Jordi Abel, Laurent Illig, Thomas Schreiber, Jens Pessler, Frank Cells Article Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD. MDPI 2022-07-24 /pmc/articles/PMC9330610/ /pubmed/35892580 http://dx.doi.org/10.3390/cells11152283 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arshad, Haroon
Siokis, Anastasios
Franke, Raimo
Habib, Aamna
Alfonso, Juan Carlos López
Poliakova, Yuliya
Lücke, Eva
Michaelis, Katina
Brönstrup, Mark
Meyer-Hermann, Michael
Bilitewski, Ursula
Vila, Jordi
Abel, Laurent
Illig, Thomas
Schreiber, Jens
Pessler, Frank
Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title_full Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title_fullStr Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title_full_unstemmed Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title_short Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
title_sort reprogramming of amino acid metabolism differs between community-acquired pneumonia and infection-associated exacerbation of chronic obstructive pulmonary disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330610/
https://www.ncbi.nlm.nih.gov/pubmed/35892580
http://dx.doi.org/10.3390/cells11152283
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