Please use this identifier to cite or link to this item:
Title: Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia
Author: 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
Keywords: Pneumònia adquirida a la comunitat
Malalties pulmonars obstructives cròniques
Community-acquired pneumonia
Chronic obstructive pulmonary diseases
Issue Date: 11-Nov-2019
Publisher: BioMed Central
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Journal of Translational Medicine, 2019, vol. 17
Related resource:
ISSN: 1479-5876
Appears in Collections:Articles publicats en revistes (ISGlobal)

Files in This Item:
File Description SizeFormat 
ArshadH_JTranslMed_2019.pdf5.01 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons