Identification of Immune Candidate Genes in Post-Sepsis Syndrome: Linking Innate Immunity to Long-Term Autoimmune...

Introduction: Post-sepsis syndrome (PSS) is marked by persistent immune dysregulation, leading to long-term complications that overlap with autoimmune responses. Uncovering key immune-related candidate genes during PSS recovery can enhance our understanding of immune mechanisms involved in post-sepsis complications and inform targeted therapeutic strategies.

The objectives of the study were to analyze the GSE46955 dataset containing 24 peripheral blood mononuclear cell samples: 8 from the sepsis stage, 8 from the recovery phase, and 6 from healthy controls; use the Linear Models for Microarray Data (limma) and Weighted Gene Co-Expression Network Analysis (WGCNA) to identify differentially expressed genes (DEGs); and further explore key genes and pathways in sepsis recovery through protein-protein interaction (PPI) networks, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment, and a lipopolysaccharide-induced mouse model.

A total of 537 DEGs were identified, showing significant expression differences between sepsis and healthy controls. CD4, C1QA, and HLA-DRA were key hub genes in the PPI network, with increased expression in recovery samples, indicating roles in immune regulation. CD4 silencing worsened sepsis and reduced survival in mice, while CD4 overexpression improved outcomes.

Our findings highlight immune candidate genes that could serve as diagnostic and therapeutic targets in PSS, shedding light on the prolonged immune responses underlying sepsis recovery. These insights support the development of interventions targeting immune dysregulation in PSS, potentially applicable to other autoimmune conditions.