Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome

Area of Science:

• Immunology
• Geriatric Medicine
• Surgical Science

Background:

• Surgery poses a significant challenge to the immune system.
• The immune response of geriatric patients to surgical procedures remains poorly understood.
• Monocytes play a crucial role in surgical recovery.

Purpose of the Study:

• To investigate the impact of elective surgery on the molecular signature of circulating CD14+ monocytes in older patients.
• To identify changes in immune-related gene expression in monocytes following joint replacement and spine surgery.
• To explore the potential of monocyte gene expression as a biomarker for surgical outcomes in the elderly.

Main Methods:

• Analysis of pre- to postoperative gene expression changes in 784 immune-related genes within monocytes.
• Recruitment of older patients undergoing elective joint replacement (N=19) or spine surgery (N=16).
• Statistical analysis of differential gene expression, including adjusted p-values and log fold changes (|logFC|).

Main Results:

• Joint replacement surgery altered 489 immune genes (adjusted p < 0.05), with 38 showing |logFC| > 1.
• Spine surgery affected 209 immune genes (adjusted p < 0.05), with 27 showing |logFC| > 1.
• In combined analysis (N=35), 471 transcripts were differentially expressed post-surgery, with 72% of those with |logFC| > 1 being downregulated, suggesting a hypoactive immune phenotype.

Conclusions:

• Elective surgery in older patients induces substantial changes in the monocyte immune gene transcriptome.
• The observed downregulation of genes suggests a potential immunocompromised or hypoactive monocyte phenotype post-surgery.
• This monocyte gene expression signature offers insights into the immune response to surgery and may serve as a biomarker for predicting outcomes in older surgical patients.