The Intestinal Immune Network for IgA Production is Involved in the Development and Progression of Sepsis: A...

Area of Science:

• Immunology
• Genomics
• Bioinformatics

Background:

• Intestinal barrier injury is a key factor in sepsis development, but its mechanisms are not fully understood.
• The "intestinal immune network for IgA production" pathway (hsa04672) is linked to intestinal barrier function.

Purpose of the Study:

• To investigate the role of the "intestinal immune network for IgA production" pathway (hsa04672) in sepsis.
• To identify diagnostic and prognostic biomarkers associated with hsa04672 in sepsis.

Main Methods:

• Integrated bulk and single-cell RNA sequencing, clinical trial, animal study, and Mendelian randomization (MR) analyses.
• Utilized machine learning for biomarker identification and Gene Set Variation Analysis (GSVA) for pathway activity assessment.
• Constructed a nomogram model based on prognostic biomarkers for sepsis prediction.

Main Results:

• Enrichment analyses confirmed hsa04672's association with sepsis.
• Identified HLA-DPA1, ITGB7, and CXCR4 as diagnostic biomarkers (AUC > 0.94) and ANKRD55, CX3CR1, GIMAP4 as prognostic biomarkers.
• Demonstrated suppressed hsa04672 activity in sepsis patients, identified sepsis subgroups with distinct prognoses, and confirmed reduced intestinal IgA in severe sepsis.
• MR analyses indicated CXCR4 as a sepsis risk factor and GIMAP4 as a risk factor for 28-day mortality in sepsis.

Conclusions:

• The "intestinal immune network for IgA production" pathway plays a significant role in sepsis pathogenesis and progression.
• Identified novel diagnostic and prognostic biomarkers for sepsis, offering potential therapeutic targets.