Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

作者：Haroon Arshad, Juan Carlos López Alfonso, Raimo Franke, Katina Michaelis, Leonardo Araujo, Aamna Habib, Yuliya Zboromyrska, Eva Lücke, Emilia Strungaru, Manas K. Akmatov, Haralampos Hatzikirou, Michael Meyer‐Hermann, Astrid Petersmann, Matthias Nauck, Mark Brönstrup, Ursula Bilitewski, Laurent Abel, Jörg Sievers, Jordi Vilà, Thomas Illig, Jens Schreiber, Frank Peßler · 发表于：Journal of Translational Medicine · 年份：2019 · DOI：10.1186/s12967-019-2112-z · 被引用次数：71 · 研究领域：Sphingolipid Metabolism and Signaling、Pneumonia and Respiratory Infections、Pharmacological Receptor Mechanisms and Effects

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 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, lysophosphatid...