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Lipopolysaccharide-binding protein: A valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?

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Abstract

Purpose

The pre-operative differentiation between periprosthetic joint infection (PJI) and aseptic loosening after total hip (THA) or knee (TKA) arthroplasty is essential for successful therapy and relies in part on the use of molecular markers. The objective of this study was to assess serum levels of lipopolysaccharide-binding protein (LBP) as a diagnostic tool for PJI and to compare its accuracy with standard tests.

Methods

One hundred and twenty patients presenting with a painful TKA or TKA with indication for surgical revision were included in this prospective, controlled, clinical trial at a single centre. Pre-operative blood and serum samples were collected and analysed for white blood cell (WBC) count, C-reactive protein (CRP) and LBP. The definite diagnosis of periprosthetic joint infection was determined on the basis of clinical, microbiological and histopathological examination.

Results

LBP showed significantly higher values in PJI compared with aseptic loosening (p < 0.001) and control (p < 0.001), with a specificity of 66 % and a sensitivity of 71 % at a cutoff value of >7 ng/ml. In combination with CRP, the positive predictive value for PJI was at 0.67; negative predictive value with both negative was at 0.77.

Discussion

Patients with PJI have elevated serum levels of LBP when compared with patients with aseptic loosening. The use of LBP in serum appears not to be a more accurate marker than CRP level in serum for detecting PJI. On the basis of these results, we cannot recommend the sole use of LBP for differentiating PJI and aseptic loosening following THA and TKA.

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References

  1. Trampuz A, Zimmerli W (2005) New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Investig Drugs 6:185–190

    PubMed  CAS  Google Scholar 

  2. Frommelt L (2004) Guidelines on antimicrobial therapy in situations of periprosthetic THR infection. Orthopade 33:822–828. doi:10.1007/s00132-004-0677-5

    Article  PubMed  CAS  Google Scholar 

  3. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351:1645–1654. doi:10.1056/NEJMra040181

    Article  PubMed  CAS  Google Scholar 

  4. Berbari E, Mabry T, Tsaras G, Spangehl M, Erwin PJ, Murad MH, Steckelberg J, Osmon D (2010) Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am Vol 92:2102–2109. doi:10.2106/JBJS.I.01199

    Article  Google Scholar 

  5. Deirmengian C, Hallab N, Tarabishy A, Della Valle C, Jacobs JJ, Lonner J, Booth RE Jr (2010) Synovial fluid biomarkers for periprosthetic infection. Clin Orthop Relat Res 468:2017–2023. doi:10.1007/s11999-010-1298-4

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gollwitzer H, Dombrowski Y, Prodinger PM, Peric M, Summer B, Hapfelmeier A, Saldamli B, Pankow F, von Eisenhart-Rothe R, Imhoff AB, Schauber J, Thomas P, Burgkart R, Banke IJ (2013) Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection. J Bone Joint Surg Am Vol 95:644–651. doi:10.2106/JBJS.L.00205

    Article  Google Scholar 

  7. Glehr M, Friesenbichler J, Hofmann G, Bernhardt GA, Zacherl M, Avian A, Windhager R, Leithner A (2013) Novel biomarkers to detect infection in revision hip and knee arthroplasties. Clin Orthop Relat Res 471:2621–2628. doi:10.1007/s11999-013-2998-3

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hundric-Haspl Z, Pecina M, Haspl M, Tomicic M, Jukic I (2006) Plasma cytokines as markers of aseptic prosthesis loosening. Clin Orthop Relat Res 453:299–304. doi:10.1097/01.blo.0000229365.57985.96

    Article  PubMed  Google Scholar 

  9. Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG (2011) New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 469:2992–2994. doi:10.1007/s11999-011-2102-9

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gollwitzer H, Diehl P, Gerdesmeyer L, Mittelmeier W (2006) Diagnostic strategies in cases of suspected periprosthetic infection of the knee. A review of the literature and current recommendations. Orthopade 35:904. doi:10.1007/s00132-006-0977-z, 906–908, 910–906

    Article  PubMed  CAS  Google Scholar 

  11. Ghanem E, Antoci V Jr, Pulido L, Joshi A, Hozack W, Parvizi J (2009) The use of receiver operating characteristics analysis in determining erythrocyte sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior to revision total hip arthroplasty. Int J Infect Dis 13:e444–e449. doi:10.1016/j.ijid.2009.02.017

    Article  PubMed  CAS  Google Scholar 

  12. Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW (2006) Periprosthetic infection: what are the diagnostic challenges? J Bone Joint Surg Am Vol 88(Suppl 4):138–147. doi:10.2106/JBJS.F.00609

    Article  Google Scholar 

  13. Toossi N, Adeli B, Rasouli MR, Huang R, Parvizi J (2012) Serum white blood cell count and differential do not have a role in the diagnosis of periprosthetic joint infection. J Arthroplast 27:51–54 e51. doi:10.1016/j.arth.2012.03.021

    Article  Google Scholar 

  14. 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 36:2932–2939

    PubMed  CAS  PubMed Central  Google Scholar 

  15. Kobayashi N, Inaba Y, Choe H, Iwamoto N, Ishida T, Yukizawa Y, Aoki C, Ike H, Saito T (2009) Rapid and sensitive detection of methicillin-resistant Staphylococcus periprosthetic infections using real-time polymerase chain reaction. Diagn Microbiol Infect Dis 64:172–176. doi:10.1016/j.diagmicrobio.2009.01.033

    Article  PubMed  CAS  Google Scholar 

  16. Morawietz L, Classen RA, Schroder JH, Dynybil C, Perka C, Skwara A, Neidel J, Gehrke T, Frommelt L, Hansen T, Otto M, Barden B, Aigner T, Stiehl P, Schubert T, Meyer-Scholten C, Konig A, Strobel P, Rader CP, Kirschner S, Lintner F, Ruther W, Bos I, Hendrich C, Kriegsmann J, Krenn V (2006) Proposal for a histopathological consensus classification of the periprosthetic interface membrane. J Clin Pathol 59:591–597. doi:10.1136/jcp.2005.027458

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Trampuz A, Hanssen AD, Osmon DR, Mandrekar J, Steckelberg JM, Patel R (2004) Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection. Am J Med 117:556–562. doi:10.1016/j.amjmed.2004.06.022

    Article  PubMed  Google Scholar 

  18. Weiss S, Geiss H, Kommerell M, Simank HG, Bernd L, Henle P (2006) Improving the diagnosis of septic arthritis by use of a pediatric blood culture system. Orthopade 35:456. doi:10.1007/s00132-005-0900-z, 458–462

    Article  PubMed  CAS  Google Scholar 

  19. Randau T, Friedrich M, Wimmer M, Reichert B, Kuberra D, Stoffel-Wagner B, Limmern A, Wirtz D, Gravius S (2014) IL-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening. PloS One Under Review

  20. Janz V, Wassilew GI, Hasart O, Matziolis G, Tohtz S, Perka C (2013) Evaluation of sonicate fluid cultures in comparison to histological analysis of the periprosthetic membrane for detecting periprosthetic joint infection. Int Orthop 37:931–936. doi:10.1007/s00264-013-1853-1

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zweigner J, Schumann RR, Weber JR (2006) The role of lipopolysaccharide-binding protein in modulating the innate immune response. Microbes Infect/Institut Pasteur 8:946–952. doi:10.1016/j.micinf.2005.10.006

    Article  CAS  Google Scholar 

  22. Geller DA, Kispert PH, Su GL, Wang SC, Di Silvio M, Tweardy DJ, Billiar TR, Simmons RL (1993) Induction of hepatocyte lipopolysaccharide binding protein in models of sepsis and the acute-phase response. Arch Surg 128:22–27, discussion 27–28

    Article  PubMed  CAS  Google Scholar 

  23. Schumann RR, Kirschning CJ, Unbehaun A, Aberle HP, Knope HP, Lamping N, Ulevitch RJ, Herrmann F (1996) The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. Mol Cell Biol 16:3490–3503

    PubMed  CAS  PubMed Central  Google Scholar 

  24. Hallatschek W, Fiedler G, Kirschning CJ, Creutzburg F, Lamping N, Nussler A, Schumann RR (2004) Inhibition of hepatic transcriptional induction of lipopolysaccharide-binding protein by transforming-growth-factor beta 1. Eur J Immunol 34:1441–1450. doi:10.1002/eji.200324874

    Article  PubMed  CAS  Google Scholar 

  25. Zweigner J, Gramm HJ, Singer OC, Wegscheider K, Schumann RR (2001) High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes. Blood 98:3800–3808

    Article  PubMed  CAS  Google Scholar 

  26. Wimmer MD, Randau TM, Petersdorf S, Pagenstert GI, Weisskopf M, Wirtz DC, Gravius S (2013) Evaluation of an interdisciplinary therapy algorithm in patients with prosthetic joint infections. Int Orthop 37:2271–2278. doi:10.1007/s00264-013-1995-1

    Article  PubMed  Google Scholar 

  27. Laffer RR, Graber P, Ochsner PE, Zimmerli W (2006) Outcome of prosthetic knee-associated infection: evaluation of 40 consecutive episodes at a single centre. Clin Microbiol Infect : Off Publ Eur Soc Clin Microbiol Infect Dis 12:433–439. doi:10.1111/j.1469-0691.2006.01378.x

    Article  CAS  Google Scholar 

  28. Krenn V, Morawietz L, Kienapfel H, Ascherl R, Matziolis G, Hassenpflug J, Thomsen M, Thomas P, Huber M, Schuh C, Kendoff D, Baumhoer D, Krukemeyer MG, Perino G, Zustin J, Berger I, Ruther W, Poremba C, Gehrke T (2013) Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses. Z Rheumatol 72:383–392. doi:10.1007/s00393-012-1099-0

    Article  PubMed  CAS  Google Scholar 

  29. Bozic KJ, Rubash HE (2004) The painful total hip replacement. Clin Orthop Relat Res 420:18–25

    Article  PubMed  Google Scholar 

  30. Bernard L, Lubbeke A, Stern R, Bru JP, Feron JM, Peyramond D, Denormandie P, Arvieux C, Chirouze C, Perronne C, Hoffmeyer P, Groupe D’Etude Sur LO (2004) Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature review. Scand J Infect Dis 36:410–416

    Article  PubMed  Google Scholar 

  31. Alijanipour P, Bakhshi H, Parvizi J (2013) Diagnosis of periprosthetic joint infection: the threshold for serological markers. Clin Orthop Relat Res 471:3186–3195. doi:10.1007/s11999-013-3070-z

    Article  PubMed  Google Scholar 

  32. Buttaro MA, Tanoira I, Comba F, Piccaluga F (2010) Combining C-reactive protein and interleukin-6 may be useful to detect periprosthetic hip infection. Clin Orthop Relat Res 468:3263–3267. doi:10.1007/s11999-010-1451-0

    Article  PubMed  PubMed Central  Google Scholar 

  33. Parvizi J, McKenzie JC, Cashman JP (2012) Diagnosis of periprosthetic joint infection using synovial C-reactive protein. J Arthroplast 27:12–16. doi:10.1016/j.arth.2012.03.018

    Article  Google Scholar 

  34. Piper KE, Fernandez-Sampedro M, Steckelberg KE, Mandrekar JN, Karau MJ, Steckelberg JM, Berbari EF, Osmon DR, Hanssen AD, Lewallen DG, Cofield RH, Sperling JW, Sanchez-Sotelo J, Huddleston PM, Dekutoski MB, Yaszemski M, Currier B, Patel R (2010) C-reactive protein, erythrocyte sedimentation rate and orthopedic implant infection. PLoS One 5:e9358. doi:10.1371/journal.pone.0009358

    Article  PubMed  PubMed Central  Google Scholar 

  35. Branescu C, Serban D, Dascalu AM, Oprescu SM, Savlovschi C (2013) Interleukin 6 and lipopolysaccharide binding protein—markers of inflammation in acute appendicitis. Chirurgia 108:206–214

    PubMed  CAS  Google Scholar 

  36. Pavare J, Grope I, Kalnins I, Gardovska D (2010) High-mobility group box-1 protein, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study. BMC Infect Dis 10:28. doi:10.1186/1471-2334-10-28

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tsalkidou EA, Roilides E, Gardikis S, Trypsianis G, Kortsaris A, Chatzimichael A, Tentes I (2013) Lipopolysaccharide-binding protein: a potential marker of febrile urinary tract infection in childhood. Pediatr Nephrol 28:1091–1097. doi:10.1007/s00467-013-2432-9

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was funded by a grant from the “Deutsch Arthrose-Hilfe e.V.” (http://www.arthrose.de/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Max J. Friedrich.

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Max J. Friedrich and Thomas M. Randau contributed equally.

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Friedrich, M.J., Randau, T.M., Wimmer, M.D. et al. Lipopolysaccharide-binding protein: A valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?. International Orthopaedics (SICOT) 38, 2201–2207 (2014). https://doi.org/10.1007/s00264-014-2351-9

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