Transcriptomic and Proteomic Characterization of the Immune Response to Elective Spinal Reconstructive Surgery: Impact of Aging and Comparisons with the Traumatic Injury Response

Abstract

BACKGROUND: Major surgery triggers trauma-like stress responses linked to age, surgery duration, and blood loss, resembling polytrauma. This similarity suggests elective surgery as a surrogate model for studying polytrauma immune responses. We investigated stress responses across age groups and compared them to those of polytrauma patients. STUDY DESIGN: Patients undergoing major spinal reconstruction surgery were divided into older (age > 65, n=5) and young (age=18-39, n=6) groups. A comparison group consisted of matched trauma patients (n=8). Blood samples were collected before, during, and after surgery. Bone marrow and peripheral blood mononuclear cells (BMMC and PBMC) were analyzed using CITEseq/scRNAseq. Plasma was subjected to dual-platform proteomic analysis (Somalogic and O-link). RESULTS: Response to polytrauma was highest within 4 hrs. By comparison, the response to surgery was highest at 24 hrs. Both insults triggered significant changes in CD14+ monocytes, with increased inflammation and lower MHC-II expression. Older patient’s CD14+ monocytes displayed higher inflammation and less MHC-II suppression; a trend also seen in BMMCs. While NK cells were markedly activated after polytrauma; NK cells were suppressed after surgery, especially in older patients. In plasma, innate immunity proteins dominated at 24 hours, shifting to adaptive immunity proteins by 6 weeks with heightened inflammation in older patients. SASP proteins were higher in older patients at baseline and further elevated during and after surgery. CONCLUSION: While both major surgery and polytrauma initiate immune and stress responses, substantial differences exist in timing and cellular profiles, suggesting major elective surgery is not a suitable surrogate for the polytrauma response. Nonetheless, distinct responses in young vs. older patients highlight the utility of elective spinal in studying patient-specific factors affecting outcomes following major elective surgery.