Sphingolipidomics in Translational Sepsis Research–Biomedical Considerations and Perspectives

Abstract

Scientific Background: Sphingolipids are a highly diverse group of lipids with respect to physicochemical properties controlling either structure, distribution, or function, all of them regulating cellular response in health and disease. Mass spectrometry, on the other hand, is an analytical technique characterizing ionized molecules or fragments thereof by mass-to-charge ratios, which has been prosperingly developed for rapid and reliable qualitative and quantitative identification of lipid species. Parallel to best performance of in-depth chromatographical separation of lipid classes, preconditions of precise quantitation of unique molecular species by preprocessing of biological samples have to be fulfilled. As a consequence, “lipid profiles” across model systems and human individuals, esp. complex (clinical) samples, have become eminent over the last couple of years due to sensitivity, specificity, and discriminatory capability. Therefore, it is significance to consider the entire experimental strategy from sample collection and preparation, data acquisition, analysis, and interpretation.Areas Covered: In this review, we outline considerations with clinical (i.e., human) samples with special emphasis on sample handling, specific physicochemical properties, target measurements, and resulting profiling of sphingolipids in biomedicine and translational research to maximize sensitivity and specificity as well as to provide robust and reproducible results. A brief commentary is also provided regarding new insights of “clinical sphingolipidomics” in translational sepsis research.Expert Opinion: The role of mass spectrometry of sphingolipids and related species (“sphingolipidomics”) to investigate cellular and compartment-specific response to stress, e.g., in generalized infection and sepsis, is on the rise and the ability to integrate multiple datasets from diverse classes of biomolecules by mass spectrometry measurements and metabolomics will be crucial to fostering our understanding of human health as well as response to disease and treatment.

Discrimination of serum metabolomics profiles in infants with sepsis, based on liquid chromatography-mass spectrometer

“…SM (d18:0/16:1(9Z)) is a sphingolipid substance on the membranes of cells that contributes to the structural integrity of those cells. It is also an essential component of signal transduction modules of critical biological reactions, such as cell division, differentiation, gene expression, and apoptosis [ 21 , 22 ]. This work found that SM (d18:0/16:1(9Z)) levels decreased significantly in the sepsis group, consistent with the previous study by Winkler et al [ 23 ], concluding that SM (d18:0/16:1(9Z)) is an accurate predictor for septic mortality [ 24 ].…”

Serum Sphingolipids Aiding the Diagnosis of Adult HIV-Negative Patients with Talaromyces marneffei Infection

“…Based on the rapid, reliable, and high sensitivity, specificity, and throughput properties of LC-MS, it is possible to characterize the sphingolipidome of large-scale clinical samples, resulting in a systemic overview of the dynamic host-parasite interaction and recognition of the SPLs that mediate pathological processes ( Lee et al., 2014 ; Chong et al., 2018 ; Thu et al., 2020 ). Several studies have reviewed the important role of SPLs in the progression of infection ( Hanada, 2005 ; Maceyka and Spiegel, 2014 ; Chong et al., 2018 ; Li et al., 2019 ; Claus and Graeler, 2020 ). For instance, elevated plasma levels of SM (d18:0/16:0), SM (d18:1/16:0) and three glycosphingolipids were observed in CAP patients ( To et al., 2016 ).…”

“…Moreover, the physiological and pathological roles of SPLs as pathogenetic elements or biomarkers of diseases were also reviewed in previous studies ( Matanes et al., 2019 ; Iessi et al., 2020 ). Due to its high sensitivity, specificity and throughput, as well as being rapid and reliable, SPL analysis by liquid chromatography-mass spectrometry (LC-MS) has become the most powerful strategy ( Becker et al., 2018 ; Claus and Graeler, 2020 ) and has been employed in discovery of biomarkers of various diseases. For instance, we discovered the characteristic SPLs that could be used as diagnostic biomarkers to differentiate different types of polycystic ovary syndrome (PCOS) in our previous study ( Li et al., 2019 ).…”