Show simple item record

dc.contributor.authorArshad, Haroon
dc.contributor.authorAlfonso, Juan Carlos López
dc.contributor.authorFranke, Raimo
dc.contributor.authorMichaelis, Katina
dc.contributor.authorAraujo, Leonardo
dc.contributor.authorHabib, Aamna
dc.contributor.authorZboromyrska, Yuliya
dc.contributor.authorLücke, Eva
dc.contributor.authorStrungaru, Emilia
dc.contributor.authorAkmatov, Manas K
dc.contributor.authorHatzikirou, Haralampos
dc.contributor.authorMeyer-Hermann, Michael
dc.contributor.authorPetersmann, Astrid
dc.contributor.authorNauck, Matthias
dc.contributor.authorBrönstrup, Mark
dc.contributor.authorBilitewski, Ursula
dc.contributor.authorAbel, Laurent
dc.contributor.authorSievers, Jorg
dc.contributor.authorVila, Jordi
dc.contributor.authorIllig, Thomas
dc.contributor.authorSchreiber, Jens
dc.contributor.authorPessler, Frank
dc.date.accessioned2019-11-27T09:16:59Z
dc.date.available2019-11-27T09:16:59Z
dc.date.issued2019-11-11
dc.identifier.citationJ Transl Med. 2019 Nov 11;17(1):365. doi: 10.1186/s12967-019-2112-z.en_US
dc.identifier.issn1479-5876
dc.identifier.pmid31711507
dc.identifier.doi10.1186/s12967-019-2112-z
dc.identifier.urihttp://hdl.handle.net/10033/622033
dc.description.abstractBACKGROUND: 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 ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers 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 differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. 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 differences 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 CAPen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/115523en_US
dc.rightsopenAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectBiomarkersen_US
dc.subjectChronic obstructive pulmonary diseaseen_US
dc.subjectCommunity-acquired pneumoniaen_US
dc.subjectGlycerophospholipidsen_US
dc.subjectInfectionen_US
dc.subjectLipidomicsen_US
dc.subjectLung diseaseen_US
dc.subjectMass spectrometryen_US
dc.subjectMetabolismen_US
dc.subjectMetabolomicsen_US
dc.subjectSphingomyelinaseen_US
dc.titleDecreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalJournal of translational medicineen_US
refterms.dateFOA2019-11-27T09:16:59Z
dc.source.journaltitleJournal of translational medicine


Files in this item

Thumbnail
Name:
Arshad et al.pdf
Size:
4.950Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

openAccess
Except where otherwise noted, this item's license is described as openAccess