FABP4 expression in neutrophils as a predictor of sepsis and SI-ARDS based on BALF transcriptome and peripheral blood validation.

Summary

Across BALF and blood cohorts, neutrophil FABP4 expression was downregulated in SI-ARDS, reducing apoptosis via PI3K/AKT signaling and associating with worse survival. Transcriptomic profiling revealed predominantly immune pathway downregulation and pathogen-specific signatures, especially with drug-resistant Klebsiella pneumoniae.

Key Findings

• Neutrophil FABP4 is significantly downregulated in SI-ARDS in BALF and validated in peripheral blood.
• FABP4 inhibition reduces neutrophil apoptosis; this resistance is reversed by PI3K/AKT inhibition.
• Low neutrophil FABP4 associates with poorer survival in SI-ARDS (cohort 3).
• Majority of overlapping DEGs are downregulated and enriched for immune pathways; pathogen-specific DEG patterns seen with drug-resistant Klebsiella pneumoniae.

Clinical Implications

Neutrophil FABP4 could support risk stratification and prognostication in sepsis/SI-ARDS, and pathway-directed modulation (e.g., PI3K/AKT) merits exploration. Clinical assays and multicenter validation are needed before adoption.

Limitations

• Initial discovery cohorts are relatively small and likely single-center
• Observational design with potential confounding; generalizability requires external validation

Future Directions

Develop and validate clinical-grade FABP4 assays; multicenter prospective studies for prognostic utility; explore therapeutic modulation of FABP4/PI3K–AKT in preclinical ARDS models.