Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia
Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/146177 |
| Acceso en línea: | https://hdl.handle.net/2445/146177 |
| Access Level: | acceso abierto |
| Palabra clave: | Pneumònia adquirida a la comunitat Malalties pulmonars obstructives cròniques Community-acquired pneumonia Chronic obstructive pulmonary diseases |
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Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumoniaArshad, HaroonLópez Alfonso, Juan CarlosFranke, RaimoMichaelis, KatinaAraujo, LeonardoHabib, AamnaZboromyrska, YuliyaLücke, EvaStrungaru, EmiliaAkmatov, Manas K.Hatzikirou, HaralamposMeyer-Hermann, MichaelPetersmann, AstridNauck, MatthiasBrönstrup, MarkBilitewski, UrsulaAbel, LaurentSievers, JorgVila Estapé, JordiIllig, ThomasSchreiber, JensPessler, FrankPneumònia adquirida a la comunitatMalalties pulmonars obstructives cròniquesCommunity-acquired pneumoniaChronic obstructive pulmonary diseasesBackground: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n=29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n=13) as a clinically important disease control, and 33 age- and sex-matched controls. Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and cer‑ amides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also difered qualitatively, e.g. by increases in selected sphingomyelins. We identifed highly accurate biomark‑ ers for CAP (AUC≤0.97) and COPD (AUC≤0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC≤0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and diferentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers refect more than merely infammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change=2.8, AUC=0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal diferences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.BioMed Central2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/146177Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1186/s12967-019-2112-zJournal of Translational Medicine, 2019, vol. 17http://dx.doi.org/10.1186/s12967-019-2112-zinfo:eu-repo/grantAgreement/EC/FP7/115523cc by (c) Arshad et al., 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1461772026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| title |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| spellingShingle |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia Arshad, Haroon Pneumònia adquirida a la comunitat Malalties pulmonars obstructives cròniques Community-acquired pneumonia Chronic obstructive pulmonary diseases |
| title_short |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| title_full |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| title_fullStr |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| title_full_unstemmed |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| title_sort |
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia |
| dc.creator.none.fl_str_mv |
Arshad, Haroon López Alfonso, Juan Carlos Franke, Raimo Michaelis, Katina Araujo, Leonardo Habib, Aamna Zboromyrska, Yuliya Lücke, Eva Strungaru, Emilia Akmatov, Manas K. Hatzikirou, Haralampos Meyer-Hermann, Michael Petersmann, Astrid Nauck, Matthias Brönstrup, Mark Bilitewski, Ursula Abel, Laurent Sievers, Jorg Vila Estapé, Jordi Illig, Thomas Schreiber, Jens Pessler, Frank |
| author |
Arshad, Haroon |
| author_facet |
Arshad, Haroon López Alfonso, Juan Carlos Franke, Raimo Michaelis, Katina Araujo, Leonardo Habib, Aamna Zboromyrska, Yuliya Lücke, Eva Strungaru, Emilia Akmatov, Manas K. Hatzikirou, Haralampos Meyer-Hermann, Michael Petersmann, Astrid Nauck, Matthias Brönstrup, Mark Bilitewski, Ursula Abel, Laurent Sievers, Jorg Vila Estapé, Jordi Illig, Thomas Schreiber, Jens Pessler, Frank |
| author_role |
author |
| author2 |
López Alfonso, Juan Carlos Franke, Raimo Michaelis, Katina Araujo, Leonardo Habib, Aamna Zboromyrska, Yuliya Lücke, Eva Strungaru, Emilia Akmatov, Manas K. Hatzikirou, Haralampos Meyer-Hermann, Michael Petersmann, Astrid Nauck, Matthias Brönstrup, Mark Bilitewski, Ursula Abel, Laurent Sievers, Jorg Vila Estapé, Jordi Illig, Thomas Schreiber, Jens Pessler, Frank |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Pneumònia adquirida a la comunitat Malalties pulmonars obstructives cròniques Community-acquired pneumonia Chronic obstructive pulmonary diseases |
| topic |
Pneumònia adquirida a la comunitat Malalties pulmonars obstructives cròniques Community-acquired pneumonia Chronic obstructive pulmonary diseases |
| description |
Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n=29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n=13) as a clinically important disease control, and 33 age- and sex-matched controls. Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and cer‑ amides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also difered qualitatively, e.g. by increases in selected sphingomyelins. We identifed highly accurate biomark‑ ers for CAP (AUC≤0.97) and COPD (AUC≤0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC≤0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and diferentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers refect more than merely infammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change=2.8, AUC=0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal diferences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/146177 |
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https://hdl.handle.net/2445/146177 |
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Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1186/s12967-019-2112-z Journal of Translational Medicine, 2019, vol. 17 http://dx.doi.org/10.1186/s12967-019-2112-z info:eu-repo/grantAgreement/EC/FP7/115523 |
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cc by (c) Arshad et al., 2019 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by (c) Arshad et al., 2019 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
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application/pdf |
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BioMed Central |
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BioMed Central |
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Articles publicats en revistes (ISGlobal) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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