Acyl-CoA-binding protein (ACBP): a poor-prognosis biomarker in sepsis and a target for disease mitigation.

Summary

ACBP/DBI is elevated in septic patients and predicts worse outcomes. In multiple murine sepsis models, genetic deletion or antibody neutralization of ACBP/DBI reduced cytokine storm, preserved organ function, restored thermoregulation, and improved survival; benefits extended to combination therapy with glucocorticoids.

Key Findings

• Plasma ACBP/DBI is elevated in septic patients and associates with organ dysfunction and higher mortality.
• Genetic deletion or antibody-mediated neutralization of ACBP/DBI mitigates cytokine storm, preserves organ function, and improves survival in endotoxemia, E. coli, and polymicrobial sepsis models.
• ACBP/DBI neutralization restores thermoregulation and enhances macrophage/granulocyte bacterial clearance in vivo and in vitro.
• Combining ACBP/DBI inhibition with glucocorticoids further enhances survival and reverses multi-organ septic shock signatures.

Clinical Implications

Supports development of anti-ACBP/DBI therapeutics (alone or with corticosteroids) and consideration of ACBP/DBI as a risk stratification biomarker in sepsis.

Limitations

• Human data are observational with unspecified sample size and lack interventional validation
• Preclinical efficacy in murine models may not directly translate to humans; safety of anti-ACBP therapy is unknown

Future Directions

First-in-human dose-finding and safety studies of anti-ACBP/DBI antibodies with biomarker-driven enrichment; combination trials with corticosteroids; mechanistic dissection of ACBP signaling in human sepsis.