Integrated Multi-Omics Analyses Identify TYMP as a Candidate Protective Immunoregulatory Marker in CD4⁺ T Cells During Sepsis.

Authors

Yanan Wang, Jianglin Zhao, Yushi Zhang, Ji Shen, Yuan Shi, Qingxiang Liu, Xuefeng Zhang

Published in

Journal of inflammation research. Volume 19. Pages 632459. Epub Sep 22, 2026.

Abstract

Cellular heterogeneity in sepsis complicates the identification of cell-specific therapeutic targets. We aimed to identify genetically supported candidate immunogenetic regulators associated with sepsis through integrative multi-omics analyses.
We conducted an integrative observational multi-omics study combining single-cell expression quantitative trait locus-based Mendelian randomization (sc-eQTL MR), bulk transcriptomic survival analysis, genetic colocalization, single-cell RNA sequencing (scRNA-seq), and a prospective observational clinical cohort. Publicly available summary-level or de-identified datasets were analyzed, including FinnGen sepsis GWAS data (GWAS ID: finn-b-O15_PUERP_SEPSIS), OneK1K sc-eQTL data, bulk transcriptomic data (GSE65682), and scRNA-seq datasets (GSE167363 and GSE151263). For prospective validation, 30 consecutive adult patients admitted to the intensive care unit who fulfilled the Sepsis-3 criteria were enrolled at the Affiliated Jiangyin Hospital of Nantong University between January 2026 and April 2026. Peripheral blood was collected within 24 hours after fulfillment of the Sepsis-3 criteria. TYMP concentrations in plasma were quantified using ELISA.
TYMP showed a nominal inverse association with sepsis susceptibility in CD4 effector memory/TEMRA cells (OR = 0.644, P = 0.008) in the exploratory MR screening, while genetic colocalization suggested a shared genetic signal with sepsis susceptibility (PPH4 = 0.78). In an independent cohort of 30 patients with sepsis, plasma TYMP levels were significantly elevated in survivors than in non-survivors (124.9 ± 20.7 vs 109.6 ± 15.1 pg/mL, P = 0.033). TYMP exhibited prognostic value for 28-day mortality (AUC = 0.701, P = 0.042), and elevated TYMP expression was associated with improved survival (HR = 0.259, P = 0.029). Single-cell and pseudotime analyses associated TYMP-expressing CD4⁺T cells with immunoregulatory transcriptional programs involving hypoxia and TGFB1 signaling. Pseudotime analysis demonstrated dynamic transcriptional reprogramming toward an immunoregulatory state.
Integrated genetic, transcriptomic, single-cell, and clinical analyses nominate TYMP as a genetically supported candidate protective immunoregulatory marker associated with CD4⁺T cells in sepsis.

PMID:
42801117
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

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