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

Author:

Bonaroti Jillian W12,Ozel Mehves12,Chen Tianmeng12,Darby Jennifer L12,Sun Xuejing123,Moheimani Hamed12,Reitz Katherine M12,Kar Upendra K12,Zuckerbraun Brian S12,Das Jishnu4,Okonkwo David O5,Billiar Timothy R12

Affiliation:

1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA.

2. Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA.

3. Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.

4. Center for Systems Immunology, Departments of Immunology and Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA.

5. Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA.

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Surgery

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