Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients.

Summary

Across discovery and validation cohorts, HDL proteomics identified pro-SFTPB as the only HDL component whose increase was significantly associated with poor ARDS prognosis. HDL pro-SFTPB levels correlated with pro-inflammatory cytokines and, when enriched in vitro, drove M1 macrophage polarization, indicating a mechanistic role in pro-inflammatory HDL remodeling.

Key Findings

• Among 102 altered HDL proteins (discovery cohort), 18 were validated; only increased HDL-associated pro-SFTPB significantly predicted poor ARDS prognosis.
• HDL-pro-SFTPB positively correlated with pro-inflammatory cytokines/chemokines and with SAA2, and negatively with PON3.
• In vitro, pro-SFTPB-enriched HDL promoted M1 polarization of monocyte-derived macrophages (THP-1).

Clinical Implications

HDL-pro-SFTPB may serve as a prognostic biomarker and a potential target to prevent pro-inflammatory HDL remodeling and M1 macrophage polarization in ARDS.

Limitations

• Sample sizes were modest in both cohorts, limiting precision and generalizability.
• Observational associations; causal in vivo validation of pro-SFTPB’s role in ARDS progression is pending.

Future Directions

Prospective validation of HDL-pro-SFTPB as a prognostic biomarker, mechanistic dissection in vivo, and exploration of interventions to modulate HDL cargo and macrophage polarization.