Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial.

Summary

In a double-blind randomized trial of 38 older adults undergoing joint replacement, perioperative infusions of a young donor plasma protein fraction significantly modulated proteomic and single-cell immune signaling responses to surgical trauma. Key inflammatory pathways (JAK-STAT, NF-κB, MAPK) were attenuated with corresponding cellular signaling changes, providing first-in-human proof of anti-inflammatory immunomodulation by young plasma components.

Key Findings

• Perioperative young plasma protein fraction altered circulating proteomic signatures (AUC 0.796, p=0.002) and single-cell immune responses (AUC 0.904, p<0.001).
• Inflammation-related pathways JAK-STAT, NF-κB, and MAPK were significantly affected (p<0.001).
• Cellular signaling showed diminished MAPK and JAK/STAT responses and increased IκB in adaptive immune cells.
• Study demonstrated first proof-of-principle of anti-inflammatory immunomodulation by young plasma components in humans.

Clinical Implications

While not ready for clinical adoption, the findings support targeted identification of active plasma factors and future trials testing perioperative immunomodulation to reduce surgical inflammation and potentially improve outcomes in older adults.

Limitations

• Small, single-center pilot with 38 participants limits generalizability and clinical outcome inference.
• Focus on mechanistic biomarkers; no hard clinical endpoints were tested.

Future Directions

Isolate and characterize active plasma factors, test dose-response and safety, and conduct larger multicenter trials evaluating clinical outcomes and interactions with anesthetic and analgesic regimens.