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The following is a summary of “Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality,” published in the December 2024 issue of Critical Care by Augustin et al. 

Researchers conducted a retrospective study to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis.  

They analyzed data from 4 adult sepsis studies and validated findings in 2 external datasets. Lipid dysregulation subphenotypes, hypolipoprotein (HYPO; low lipoproteins, increased mortality) and normolipoprotein (NORMO; higher lipoproteins, lower mortality), were examined. Leukocytes collected within 24 hours of sepsis underwent RNA sequencing (RNAseq), and shotgun plasma lipidomics was performed.  

The results showed that of 288 patients, 43% were HYPO, and 57% were NORMO and HYPO patients had higher median SOFA scores (9 vs 5, P < 0.001), greater vasopressor use (67% vs 34%, P < 0.001), and higher 28-day mortality (30% vs 16%, P = 0.004). Leukocyte RNA sequencing identified 7 upregulated lipid metabolism genes in patients with HYPO (PCSK9, DHCR7, LDLR, ALOX5, PLTP, FDFT1, and MSMO1) compared to NORMO. Lipidomics showed lower levels of cholesterol esters (CE, adjusted P < 0.001), lysophosphatidylcholines (LPC, adjusted P = 0.001), and sphingomyelins (SM, adjusted P < 0.001) in HYPO. In patients with HYPO, DHCR7 expression correlated with decreases in CE, LPC, and SM (P < 0.01), while upregulation of PCSK9, MSMO1, DHCR7, PLTP, and LDLR correlated with lower LPC (P < 0.05). The DHCR7, ALOX5, and LDLR were correlated with reduced SM (P < 0.05). Mortality and phenotype comparisons in 2 external datasets (N = 824 patients) confirmed 6 of the 7 upregulated lipid genes (PCSK9, DHCR7, ALOX5, PLTP, LDLR, and MSMO1).  

Investigators concluded a genetic signature characterized by 7 lipid metabolism genes, with 5 genes in patients with HYPO sepsis strongly correlated with low levels of cholesterol esters, lysophosphatidylcholines, and sphingomyelins involved in cholesterol storage and innate immunity, was identified. 

Source: ccforum.biomedcentral.com/articles/10.1186/s13054-024-05216-3