Skip to main content

Advertisement

SpringerLink
Log in

Flow cytometry as a diagnostic tool for identifying total hip arthroplasty loosening and differentiating between septic and aseptic cases

  • Original Article • HIP - ARTHROPLASTY
  • Published:
European Journal of Orthopaedic Surgery & Traumatology Aims and scope Submit manuscript

Abstract

Purpose

Implant loosening represents one of the major factors of total hip arthroplasty (THA) failure. The purpose of this study was to identify specific markers indicative of septic and aseptic loosening in patients that underwent THA.

Methods

Flow cytometry was performed in blood samples of 20 patients with loosening (10 septic/10 aseptic). Additional ten healthy individuals served as a control group. The expression of surface receptors and cytoplasmic molecules in patients that underwent THA was quantified. CD62L, CD18, CD11a, CD11b and CD11c expressions were evaluated and correlated with the presence of loosening. Also, a comparison between septic and aseptic THA loosening characteristics was performed.

Results

The mean fluorescence intensity (MFI) for CD18 was significantly decreased on all leukocytes subsets in both septic and aseptic loosening compared to control group (p < 0.005 in all occasions). Patients with aseptic loosening showed increased MFI for CD11b in granulocytes and for CD11c in monocytes and granulocytes compared to the control and aseptic group (p = 0.02 and p = 0.005, respectively). In patients with septic loosening, an increase in MFI for CD11c was observed in monocytes only compared to control group (p = 0.03). The comparison between aseptic and septic loosening showed significantly lower CD18 MFI value in granulocytes for aseptic loosening (p = 0.008).

Conclusions

CD11 and CD18 MFI values appear to be indicative of loosening in THAs. Flow cytometry markers can be used to identify THA loosening, as well as to differentiate between septic and aseptic cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Holt G, Murnaghan C, Reilly J, Meek RM (2007) The biology of aseptic osteolysis. Clin Orthop Relat Res 460:240–252. doi:10.1097/BLO.0b013e31804b4147

    CAS  PubMed  Google Scholar 

  2. Berry DJ, Harmsen WS, Cabanela ME, Morrey BF (2002) Twenty-five-year survivorship of two thousand consecutive primary Charnley total hip replacements: factors affecting survivorship of acetabular and femoral components. J Bone Joint Surg Am 84-A(2):171–177

    PubMed  Google Scholar 

  3. Pizzoferrato A, Ciapetti G, Stea S, Toni A (1991) Cellular events in the mechanisms of prosthesis loosening. Clin Mater 7(1):51–81

    Article  CAS  PubMed  Google Scholar 

  4. Bi Y, Van De Motter RR, Ragab AA, Goldberg VM, Anderson JM, Greenfield EM (2001) Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclasts. J Bone Joint Surg Am 83-A(4):501–508

    CAS  PubMed  Google Scholar 

  5. Hallab NJ, Anderson S, Stafford T, Glant T, Jacobs JJ (2005) Lymphocyte responses in patients with total hip arthroplasty. J Orthop Res 23(2):384–391. doi:10.1016/j.orthres.2004.09.001

    Article  CAS  PubMed  Google Scholar 

  6. Temmerman OP, Raijmakers PG, Berkhof J, Hoekstra OS, Teule GJ, Heyligers IC (2005) Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis. J Bone Joint Surg Br 87(6):781–785. doi:10.1302/0301-620X.87B6.15625

    Article  CAS  PubMed  Google Scholar 

  7. Roder C, Eggli S, Aebi M, Busato A (2003) The validity of clinical examination in the diagnosis of loosening of components in total hip arthroplasty. J Bone Joint Surg Br 85(1):37–44

    Article  CAS  PubMed  Google Scholar 

  8. Atkins BL, Athanasou N, Deeks JJ, Crook DW, Simpson H, Peto TE, McLardy-Smith P, Berendt AR (1998) Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group. J Clin Microbiol 36(10):2932–2939

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Lin RY, Astiz ME, Saxon JC, Rackow EC (1993) Altered leukocyte immunophenotypes in septic shock. Studies of HLA-DR, CD11b, CD14, and IL-2R expression. Chest 104(3):847–853

    Article  CAS  PubMed  Google Scholar 

  10. Gonzalez-Amaro R, Sanchez-Madrid F (1999) Cell adhesion molecules: selectins and integrins. Crit Rev Immunol 19(5–6):389–429

    CAS  PubMed  Google Scholar 

  11. Bilsland CA, Diamond MS, Springer TA (1994) The leukocyte integrin p150, 95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain. J Immunol 152(9):4582–4589

    CAS  PubMed  Google Scholar 

  12. Stacker SA, Springer TA (1991) Leukocyte integrin P150, 95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. J Immunol 146(2):648–655

    CAS  PubMed  Google Scholar 

  13. Georgakopoulos T, Moss ST, Kanagasundaram V (2008) Integrin CD11c contributes to monocyte adhesion with CD11b in a differential manner and requires Src family kinase activity. Mol Immunol 45(13):3671–3681. doi:10.1016/j.molimm.2008.04.021

    Article  CAS  PubMed  Google Scholar 

  14. Prieto J, Eklund A, Patarroyo M (1994) Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol 156(1):191–211. doi:10.1006/cimm.1994.1164

    Article  CAS  PubMed  Google Scholar 

  15. Moazzam F, DeLano FA, Zweifach BW, Schmid-Schonbein GW (1997) The leukocyte response to fluid stress. Proc Natl Acad Sci USA 94(10):5338–5343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Fukuda S, Schmid-Schonbein GW (2003) Regulation of CD18 expression on neutrophils in response to fluid shear stress. Proc Natl Acad Sci USA 100(23):13152–13157. doi:10.1073/pnas.2336130100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Hughes BJ, Hollers JC, Crockett-Torabi E, Smith CW (1992) Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell locomotion. J Clin Investig 90(5):1687–1696. doi:10.1172/JCI116041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Palecanda A, Walcheck B, Bishop DK, Jutila MA (1992) Rapid activation-independent shedding of leukocyte L-selectin induced by cross-linking of the surface antigen. Eur J Immunol 22(5):1279–1286. doi:10.1002/eji.1830220524

    Article  CAS  PubMed  Google Scholar 

  19. Crockett-Torabi E, Sulenbarger B, Smith CW, Fantone JC (1995) Activation of human neutrophils through L-selectin and Mac-1 molecules. J Immunol 154(5):2291–2302

    CAS  PubMed  Google Scholar 

  20. Kishimoto TK, Jutila MA, Butcher EC (1990) Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci USA 87(6):2244–2248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Kahn J, Ingraham RH, Shirley F, Migaki GI, Kishimoto TK (1994) Membrane proximal cleavage of L-selectin: identification of the cleavage site and a 6-kD transmembrane peptide fragment of L-selectin. J Cell Biol 125(2):461–470

    Article  CAS  PubMed  Google Scholar 

  22. Koulouvaris P, Ly K, Ivashkiv LB, Bostrom MP, Nestor BJ, Sculco TP, Purdue PE (2008) Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis. J Orthop Res 26(1):106–116. doi:10.1002/jor.20486

    Article  CAS  PubMed  Google Scholar 

  23. Guenther R, Morawietz L, Friederich M, Gehrke T, Frommelt L, Schroder JH, Krenn V (2005) Expression of CD9, CD11b, CD18, CD52 and PDGFR-beta in the interface membrane of loose endoprostheses. Pathol Res Pract 201(6):435–442

    Article  CAS  PubMed  Google Scholar 

  24. Morawietz L, Weimann A, Schroeder JH, Kuban RJ, Ungethuem U, Kaps C, Slevogt H, Gehrke T, Krukemeyer MG, Krenn V (2008) Gene expression in endoprosthesis loosening: Chitinase activity for early diagnosis? J Orthop Res 26(3):394–403. doi:10.1002/jor.20485

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Haematology Laboratory - Unit of Molecular Biology, University Hospital of Ioannina, Ioannina, Greece

    Maria Ovrenovits & Georgios Vartholomatos

  2. Department of Orthopaedic Surgery, University of Ioannina, Ioannina, Greece

    Emilios E. Pakos, Nikolaos K. Paschos, Theodoros A. Xenakis & Grigorios I. Mitsionis

  3. Department of Biomedical Engineering, University of California, Davis, CA, USA

    Nikolaos K. Paschos

Authors
  1. Maria Ovrenovits
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilios E. Pakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Georgios Vartholomatos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nikolaos K. Paschos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Theodoros A. Xenakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Grigorios I. Mitsionis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikolaos K. Paschos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ovrenovits, M., Pakos, E.E., Vartholomatos, G. et al. Flow cytometry as a diagnostic tool for identifying total hip arthroplasty loosening and differentiating between septic and aseptic cases. Eur J Orthop Surg Traumatol 25, 1153–1159 (2015). https://doi.org/10.1007/s00590-015-1661-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00590-015-1661-y

Keywords

Search

Navigation