Skip to main content

Cellular immunophenotype of major spine surgery in adults

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Availability of data

Data are not available for sharing.

References

  1. Bess S, Line B, Fu KM et al (2016) The health impact of symptomatic adult spinal deformity: comparison of deformity types to United States Population norms and chronic diseases. Spine (Phila Pa 1976) 41:224–233. https://doi.org/10.1097/BRS.0000000000001202

    Article  Google Scholar 

  2. Francis RS (1988) Scoliosis screening of 3,000 college-aged women. The Utah Study–phase 2. Phys Ther 68:1513–1516

    CAS  PubMed  Google Scholar 

  3. Kebaish KM, Neubauer PR, Voros GD et al (2011) Scoliosis in adults aged forty years and older: prevalence and relationship to age, race, and gender. Spine (Phila Pa 1976) 36:731–736. https://doi.org/10.1097/BRS.0b013e3181e9f120

    Article  Google Scholar 

  4. Schwab F, Dubey A, Gamez L et al (2005) Adult scoliosis: prevalence, SF-36, and nutritional parameters in an elderly volunteer population. Spine (Phila Pa 1976) 30:1082–1085. https://doi.org/10.1097/01.brs.0000160842.43482.cd

    Article  Google Scholar 

  5. Diebo BG, Shah NV, Boachie-Adjei O et al (2019) Adult spinal deformity. Lancet 394:160–172. https://doi.org/10.1016/S0140-6736(19)31125-0

    Article  PubMed  Google Scholar 

  6. Lin E, Calvano SE, Lowry SF (2000) Inflammatory cytokines and cell response in surgery. Surgery 127:117–126. https://doi.org/10.1067/msy.2000.101584

    CAS  Article  PubMed  Google Scholar 

  7. Stoecklein VM, Osuka A, Lederer JA (2012) Trauma equals danger–damage control by the immune system. J Leukoc Biol 92:539–551. https://doi.org/10.1189/jlb.0212072

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Gaudilliere B, Fragiadakis GK, Bruggner RV et al (2014) Clinical recovery from surgery correlates with single-cell immune signatures. Sci Transl Med 6:255ra131. https://doi.org/10.1126/scitranslmed.3009701

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Peng L, Xu L, Ouyang W (2013) Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One 8:e79624. https://doi.org/10.1371/journal.pone.0079624

    Article  PubMed  PubMed Central  Google Scholar 

  10. Levine ME, Lu AT, Quach A et al (2018) An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY) 10:573–591. https://doi.org/10.18632/aging.101414

    Article  Google Scholar 

  11. Spinella PC, Thomas KA, Turnbull IR et al (2020) The immunologic effect of early intravenous two and four gram bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding (TAMPITI): a randomized, double-blind, placebo-controlled, single-center trial. Front Immunol 11:2085. https://doi.org/10.3389/fimmu.2020.02085

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Krug A, Veeraswamy R, Pekosz A et al (2003) Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J Exp Med 197:899–906. https://doi.org/10.1084/jem.20021091

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Steinman RM, Kaplan G, Witmer MD et al (1979) Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med 149:1–16. https://doi.org/10.1084/jem.149.1.1

    CAS  Article  PubMed  Google Scholar 

  14. Menges P, Kessler W, Kloecker C et al (2012) Surgical trauma and postoperative immune dysfunction. Eur Surg Res 48:180–186. https://doi.org/10.1159/000338196

    CAS  Article  PubMed  Google Scholar 

  15. Livingston DH, Appel SH, Wellhausen SR et al (1988) Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch Surg 123:1309–1312. https://doi.org/10.1001/archsurg.1988.01400350023002

    CAS  Article  PubMed  Google Scholar 

  16. Sachse C, Prigge M, Cramer G et al (1999) Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns. Clin Chem Lab Med 37:193–198. https://doi.org/10.1515/CCLM.1999.036

    CAS  Article  PubMed  Google Scholar 

  17. Turina M, Dickinson A, Gardner S et al (2006) Monocyte HLA-DR and interferon-gamma treatment in severely injured patients—a critical reappraisal more than a decade later. J Am Coll Surg 203:73–81. https://doi.org/10.1016/j.jamcollsurg.2006.03.010

    Article  PubMed  Google Scholar 

  18. Vester H, Dargatz P, Huber-Wagner S et al (2015) HLA-DR expression on monocytes is decreased in polytraumatized patients. Eur J Med Res 20:84. https://doi.org/10.1186/s40001-015-0180-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Mokart D, Textoris J, Chow-Chine L et al (2011) HLA-DR and B7–2 (CD86) monocyte expressions after major cancer surgery: profile in sepsis. Minerva Anestesiol 77:522–527

    CAS  PubMed  Google Scholar 

  20. Miller AC, Rashid RM, Elamin EM (2007) The “T” in trauma: the helper T-cell response and the role of immunomodulation in trauma and burn patients. J Trauma 63:1407–1417. https://doi.org/10.1097/TA.0b013e31815b839e

    CAS  Article  PubMed  Google Scholar 

  21. Verdonk F, Einhaus J, Tsai AS et al (2021) Measuring the human immune response to surgery: multiomics for the prediction of postoperative outcomes. Curr Opin Crit Care 27:717–725. https://doi.org/10.1097/MCC.0000000000000883

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by a Grant from the Scoliosis Research Society.

Author information

Authors and Affiliations

Authors

Contributions

Conception/design: IRT, AF, EPF, MPK. Acquisition of data: IRP, AH, AF, EPF, SG, S-WH, MPK. Analysis: IRT, AH, AF. Interpretation: IRT, AH, AF, MPK. Drafting/revising: IRT, AH, AF, EPF, MPK. Final approval: IRP, AH, AF, EPF, SG, S-WH, MPK. Agree to accountability: IRP, AH, AF, EPF, SG, S-WH, MPK.

Corresponding author

Correspondence to Michael P. Kelly.

Ethics declarations

Conflict of interest

Dr. Kelly reports institutional support from the Setting Scoliosis Straight Foundation. Drs. Turnbull, Hess, Fuchs, Frazier, Ghosh, and Hughes report no conflicts of interest.

Ethical standards

This project was approached by the local Institutional Review Board (IRB#201811009).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Turnbull, I.R., Hess, A., Fuchs, A. et al. Cellular immunophenotype of major spine surgery in adults. Spine Deform (2022). https://doi.org/10.1007/s43390-022-00524-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s43390-022-00524-6

Keywords

  • Adult spinal deformity
  • Cytometry
  • Cytof
  • Immunophenotype