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

Summary

Plasma ACBP/DBI is elevated in sepsis and associates with organ dysfunction and mortality. Genetic deletion or antibody neutralization of ACBP/DBI reduces cytokine storm, restores thermoregulation, improves bacterial clearance, and lowers mortality across endotoxemia, E. coli, and polymicrobial sepsis models, with additive benefit when combined with glucocorticoids.

Key Findings

• Plasma ACBP/DBI levels are elevated in septic patients and correlate with organ dysfunction and mortality.
• Genetic deletion or monoclonal antibody neutralization of ACBP/DBI mitigates cytokine storm, preserves organ function, restores thermoregulation, and reduces mortality in endotoxemia, E. coli, and polymicrobial sepsis models.
• ACBP/DBI inhibition enhances bacterial clearance by macrophages and granulocytes; combination with glucocorticoids further improves survival and reverses multi-organ shock signatures.

Clinical Implications

ACBP/DBI could serve as a prognostic biomarker and a therapeutic target. Antibody-based ACBP/DBI neutralization, potentially combined with corticosteroids, warrants clinical translation and may redefine adjunctive therapy in septic shock.

Limitations

• Preclinical efficacy without human interventional trial data; translational gaps remain.
• Safety, off-target effects, and optimal dosing of ACBP/DBI neutralization are uncharacterized in humans.

Future Directions

Conduct first-in-human dose-escalation studies of ACBP/DBI neutralizing antibodies with biomarker-guided enrichment; evaluate combinations with corticosteroids and standard care in septic shock.