Language
English
Publication Date
3-5-2026
Journal
The Journal of Applied Laboratory Medicine
DOI
10.1093/jalm/jfaf179
PMID
41400245
PMCID
PMC12951321
PubMedCentral® Posted Date
12-16-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.
Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.
Results: At ARIC visit three, 669 proteins were associated with the risk of sepsis; 175 were replicated at visit 5. Of these, 90 were validated in the CHS. The top 20 proteins ranked by P value were relevant to acute inflammatory signaling in innate immunity. Pathway analyses implicated activation of pro-inflammatory pathways (e.g., cytokine storm signaling) as well as inhibition of anti-inflammatory pathways (e.g., liver X receptor/retinoid X receptor [LXR/RXR] activation), which also play relevant roles in lipid metabolism.
Conclusions: In this analysis, levels of acute inflammatory proteins measured during routine visits were associated with the subsequent incidence of sepsis. An increased risk of sepsis associated with the inhibition of anti-inflammatory pathways, such as LXR/RXR warrants further mechanistic investigation.
Keywords
Humans, Sepsis, Female, Male, Aged, Atherosclerosis, Proteomics, Middle Aged, Blood Proteins, Biomarkers, Risk Factors
Published Open-Access
yes
Recommended Citation
Ishigami, Junichi; Hu, Xiao; Schlosser, Pascal; et al., "Proteomics Analysis of Plasma for Risk of Sepsis: Findings from the Atherosclerosis Risk in Communities Study" (2026). Faculty, Staff and Students Publications. 6687.
https://digitalcommons.library.tmc.edu/baylor_docs/6687