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Published in: International Orthopaedics 10/2014

01-10-2014 | Original Paper

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

Authors: Max J. Friedrich, Thomas M. Randau, Matthias D. Wimmer, Ben Reichert, Dominik Kuberra, Birgit Stoffel-Wagner, Dieter C. Wirtz, Sascha Gravius

Published in: International Orthopaedics | Issue 10/2014

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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.
Literature
1.
go back to reference Trampuz A, Zimmerli W (2005) New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Investig Drugs 6:185–190PubMed Trampuz A, Zimmerli W (2005) New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Investig Drugs 6:185–190PubMed
4.
go back to reference 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 CrossRef 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 CrossRef
6.
go back to reference 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 CrossRef 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 CrossRef
9.
go back to reference 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 PubMedCrossRefPubMedCentral 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 PubMedCrossRefPubMedCentral
10.
go back to reference 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, 910–906PubMedCrossRef 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, 910–906PubMedCrossRef
11.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
12.
13.
14.
go back to reference 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 36:2932–2939PubMedPubMedCentral 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 36:2932–2939PubMedPubMedCentral
15.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
16.
go back to reference 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 PubMedCrossRefPubMedCentral 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 PubMedCrossRefPubMedCentral
19.
go back to reference 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 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.
22.
go back to reference 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 27–28PubMedCrossRef 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 27–28PubMedCrossRef
23.
go back to reference 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 16:3490–3503PubMedPubMedCentral 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 16:3490–3503PubMedPubMedCentral
24.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
25.
go back to reference 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 98:3800–3808PubMedCrossRef 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 98:3800–3808PubMedCrossRef
26.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
27.
go back to reference 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 CrossRef 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 CrossRef
28.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
29.
30.
go back to reference 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 36:410–416PubMedCrossRef 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 36:410–416PubMedCrossRef
34.
go back to reference 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 PubMedCrossRefPubMedCentral 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 PubMedCrossRefPubMedCentral
35.
go back to reference Branescu C, Serban D, Dascalu AM, Oprescu SM, Savlovschi C (2013) Interleukin 6 and lipopolysaccharide binding protein—markers of inflammation in acute appendicitis. Chirurgia 108:206–214PubMed Branescu C, Serban D, Dascalu AM, Oprescu SM, Savlovschi C (2013) Interleukin 6 and lipopolysaccharide binding protein—markers of inflammation in acute appendicitis. Chirurgia 108:206–214PubMed
36.
go back to reference 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 PubMedCrossRefPubMedCentral 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 PubMedCrossRefPubMedCentral
37.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
Metadata
Title
Lipopolysaccharide-binding protein: A valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?
Authors
Max J. Friedrich
Thomas M. Randau
Matthias D. Wimmer
Ben Reichert
Dominik Kuberra
Birgit Stoffel-Wagner
Dieter C. Wirtz
Sascha Gravius
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 10/2014
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-014-2351-9

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