Nonsevere Burn Induces a Prolonged Systemic Metabolic Phenotype Indicative of a Persistent Inflammatory Response Postinjury

Abstract

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of a nonsevere burn injury, longitudinal plasma was collected from adults (n = 35) who presented at hospital with a nonsevere burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from nonburn control participants (n = 14). Samples underwent multiplatform metabolic phenotyping using 1 H nuclear magnetic resonance spectroscopy and liquid chromatographymass spectrometry to quantify 112 lipoprotein and glycoprotein signatures and 852 lipid species from across 20 subclasses. Multivariate data modeling (orthogonal projections to latent structures-discriminate analysis; OPLS-DA) revealed alterations in lipoprotein and lipid metabolism when comparing the baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann−Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value < 1.0e −4 ), low density lipoprotein-2 subfractions (variable importance in projection score; VIP > 6.83e −1 ) and monoacyglyceride (20:4) (p-value < 1.0e −4 ) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP > 7.75e −1 ), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols, and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of a nonsevere burn injury. The phenotype is indicative of an acute inflammatory profile that continues to be sustained postinjury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have an elevated incidence postburn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalize intervention strategies, and improve acute care, reducing the risk of chronic comorbidity.

Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes

“…25,28 We have also shown that the SPC regions change differently in nonsevere burns patients and remain perturbed at 6 weeks post-injury. 77 At admission into ICU, GlycA and GlycB values in sepsis and septic shock patients were significantly different from those of the healthy controls but were not elevated in the ICU patients who did not develop sepsis. However, the sepsis patients were significantly different from the ICU patients who did not develop sepsis (Figure 3A,B).…”

“…SPC signals arise from the trimethylammonium headgroups of phospholipids in lipoprotein subcompartments, where SPC 1 represents the phospholipid content of HDL4, SPC 2 is the phospholipid of HDL1–3, and SPC 3 is the phospholipid from LDL . We have previously shown with SARS-CoV-2 infection that the relative levels of glycoproteins and SPC gives insight into the inflammatory status of a patient where the glycoproteins are increased and SPC decreased in comparison to healthy control samples. , We have also shown that the SPC regions change differently in nonsevere burns patients and remain perturbed at 6 weeks post-injury …”

“… 25 , 28 We have also shown that the SPC regions change differently in nonsevere burns patients and remain perturbed at 6 weeks post-injury. 77 …”

Rapid and Self-Administrable Capillary Blood Microsampling Demonstrates Statistical Equivalence with Standard Venous Collections in NMR-Based Lipoprotein Analysis

“…SPC has also been shown to decrease during acute inflammation whilst GlycA and GlyB demonstrate increases, hence, the SPC/Glyc (total) ratio has been proposed as a marker of inflammation 22,23 . Of the latter two, the SPC signal refers to trimethylammonium residues in supramolecular phospholipid components of lipoproteins, which result in three signal components: SPC1, SPC2, and SPC3, representing the phospholipid content of HDL-4, phospholipids from HDL-1,2 and 3, and phospholipids from LDL particles, respectively 24 . And Glyc refers to the N-acetyl methyl group signals which include GlycA and GlycB, which represent glycosylated amino sugars in side chains of a composite of five main acute phase glycoproteins: α-1-acid glycoprotein, α-1-antichymotrypsin, α-1-antitrypsin, haptoglobin, and transferrin that are associated with inflammation 24 .…”

Celebrating Women in Proteomics and Metabolomics

“…Offering another valuable example of an integrative proteomic and metabolomic study, a paper led by Melissa Pergande from the group of Ying Ge presents a characterization of molecular signatures associated with age-related loss of skeletal muscle mass in rhesus monkeys, identifying metabolic signatures of sarcopenia . A longitudinal study was also conducted by Monique Ryan from the group of Nicola Gray to understand nonsevere burn injury in adults, discovering metabolic signatures plasma samples reflective of chronic inflammatory states …”