Isaiah R Turnbull1, Annie Hess1, Anja Fuchs1, Elfaridah P Frazier2, Sarbani Ghosh1, Shin-Wen Hughes1, Michael P Kelly3,4. 1. Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA. 2. Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA. 3. Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA. mpkspine@gmail.com. 4. Rady Children's Hospital, University of California, San Diego, San Diego, CA, USA. mpkspine@gmail.com.
Abstract
PURPOSE: ASD reconstructions are a major, sterile traumatic insult, likely causing perturbations to the immune systems. The immune response to surgery is associated with outcomes. The purpose of this study was to examine for a detectable immune signature associated with ASD surgery. METHODS: Consecutive patients undergoing ASD surgery were approached and enrolled. Peripheral blood was drawn before incision, 4 h after, and 24 h after incision. Blood was stabilized and comprehensive flow cytometric immunophenotyping performed. Leukocyte population frequency, absolute number and activation marker expression were defined. Immunologic features were defined and analyzed by hierarchical clustering and principal component analysis (PCA). Changes over time were evaluated by repeated measures ANOVA (RMANOVA) and were corrected for a 1% false discovery rate. Post hoc testing was by Dunn's test. p values of < = 0.05 were considered significant. RESULTS: Thirteen patients were enrolled; 11(85%) F, 65.4 years (± 7.5), surgical duration 418 ± 83 min, EBL 1928 ± 1253 mL. Hierarchical clustering and PCA found consistent time from incision-dependent changes. HLA-DR and activating co-stimulatory molecule CD86 were depressed at 4 h and furthermore at 24 h on monocyte surfaces. CD4 + HLA-DR + T cells, but not CD8 +, increased over time with increased expression of PD-1 at 4 and 24 h. CONCLUSIONS: Despite surgery and patient heterogeneity, we identified an immune signature associated with the sterile trauma of ASD surgery. Circulating leukocyte populations change in composition and signaling protein expression after incision and persisting to 24 h after incision, suggesting an immunocompromised state. Further work may determine relationships between this state and poor outcomes after surgery.
PURPOSE: ASD reconstructions are a major, sterile traumatic insult, likely causing perturbations to the immune systems. The immune response to surgery is associated with outcomes. The purpose of this study was to examine for a detectable immune signature associated with ASD surgery. METHODS: Consecutive patients undergoing ASD surgery were approached and enrolled. Peripheral blood was drawn before incision, 4 h after, and 24 h after incision. Blood was stabilized and comprehensive flow cytometric immunophenotyping performed. Leukocyte population frequency, absolute number and activation marker expression were defined. Immunologic features were defined and analyzed by hierarchical clustering and principal component analysis (PCA). Changes over time were evaluated by repeated measures ANOVA (RMANOVA) and were corrected for a 1% false discovery rate. Post hoc testing was by Dunn's test. p values of < = 0.05 were considered significant. RESULTS: Thirteen patients were enrolled; 11(85%) F, 65.4 years (± 7.5), surgical duration 418 ± 83 min, EBL 1928 ± 1253 mL. Hierarchical clustering and PCA found consistent time from incision-dependent changes. HLA-DR and activating co-stimulatory molecule CD86 were depressed at 4 h and furthermore at 24 h on monocyte surfaces. CD4 + HLA-DR + T cells, but not CD8 +, increased over time with increased expression of PD-1 at 4 and 24 h. CONCLUSIONS: Despite surgery and patient heterogeneity, we identified an immune signature associated with the sterile trauma of ASD surgery. Circulating leukocyte populations change in composition and signaling protein expression after incision and persisting to 24 h after incision, suggesting an immunocompromised state. Further work may determine relationships between this state and poor outcomes after surgery.
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