Sepsis is a life-threatening condition caused by a dysregulated host response to infection, and its pathogenesis is closely linked to immune dysregulation and inflammation. Aconitate decarboxylase 1 (ACOD1) and its metabolite itaconate are key regulators of immunometabolism, but their roles in modulating immune cell function and maintaining immune homeostasis in sepsis have not been fully elucidated. In the GSE185263 dataset, we found that ACOD1 mRNA expression was significantly elevated in the blood of sepsis patients compared to controls. Functional enrichment (GO/KEGG), gene set enrichment (GSEA), and immune-cell infiltration analyses showed that higher ACOD1 expression was associated with inflammatory and interferon-related pathways and greater inferred M1 macrophage infiltration. Protein–protein interaction network analysis linked ACOD1 to proteins involved in glucose and amino acid metabolism, providing hypothesis-generating insight into its potential metabolic context. We subsequently examined ACOD1 mRNA expression in a prospective, single-center cohort consisting of 35 ICU patients with sepsis and 10 healthy controls. ACOD1 was up-regulated in sepsis and positively correlated with SOFA, APACHE II and DIC scores, and higher expression was associated with lower 28-day survival. In this exploratory cohort, ACOD1 emerged as a candidate biomarker reflecting sepsis severity, immune status and prognosis, but its performance requires validation in larger multi-center studies. Clinical trial number Not applicable.
Xiong et al. (Wed,) studied this question.