Editorial highlights the relevance of immune cell morphology and gene signatures for sepsis diagnosis and treatment.
The transcriptome underpins the morphology and function of immune cells. By integrating high-throughput sequencing with machine learning, studies have identified key sepsis-related immune regulatory genes. Yang et al. analyzed 1,166 samples, developing a 28-gene signature (AUC=0.970) distinguishing sepsis from health controls and a 13-gene signature (AUC=1.000) differentiating sepsis from SIRS.PRKACB, a crucial myeloid-associated hub gene downregulated in sepsis, is primarily expressed in macrophages. Reduced expression of PRKACB enhances TNF-α/IL-1β release and impairs the viability of macrophages, making it a target for early diagnosis and immunotherapy. Furthermore, Cheng et al. identified three critical transcriptional biomarkers (BMX, GRB10, and GADD45A) with robust diagnostic performance. These hub genes were associated with immune response, as evidenced by the significant correlation with infiltrating immune cells. These authors not only delineated potential regulatory mechanisms via mRNA-miRNA-lncRNA interaction networks, but also predicted candidate drugs targeting the above 3 biomarkers. The above breakthroughs pinpointed the promising diagnostic and therapeutic significance of immunomorphological biomarkers in transcriptional level.The heterogeneity of immune cells contributes to different responses to sepsis treatment. Pi et al. revealed reduced regulatory interactions between naive Treg and PD1 + CD152 + TIGIT + effector memory CD4 + T cells in sepsis through mass cytometry.A novel subset signature featured by expanded CD45RA -CX3CR1 + CTLA4 + CD4 + T cells, CD45RA -17A + CD4 + T cells, CD15 + CD14 + monocytes, and Ki67 + B cells, yielded AUC=0.90 (discovery) and 0.94 (validation), thereby enabling precise immunophenotypic subtyping. To further investigate the underlying mechanisms, the relationship between
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Xie et al. (2026) studied this question.
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