Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis

  • Giovanni BalatoEmail author
  • Vincenzo de Matteo
  • Tiziana Ascione
  • Sigismondo Luca Di Donato
  • Cristiano De Franco
  • Francesco Smeraglia
  • Andrea Baldini
  • Massimo Mariconda
Orthopaedic Surgery



Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection.

Materials and methods

We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated.


We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83–0.94) and 0.95 (0.92–0.96), respectively. The area under the curve (AUC) was 0.94 (0.92–0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93–0.99) and 0.96 (95% CI 0.94–0.98), respectively; qualitative test 0.83 (95% CI 0.73–0.91) and 0.94 (95% CI 0.89–0.97), respectively.

The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172–3600.702 versus 100.9, 95% CI 30.1–338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95–0.99) and 0.91 (0.88–0.99), respectively.


Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.


α-Defensin Prosthetic joint infection Hip Knee 



The authors received no funding for this project.

Compliance with ethical standards

Conflict of interest

One author of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. The others authors have no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Lavernia C, Lee DJ, Hernandez VH (2006) The increasing financial burden of knee revision surgery in the United States. Clin Orthop Relat Res 446:221–226CrossRefGoogle Scholar
  2. 2.
    Bozic KJ, Kurtz SM, Lau E, Ong K, Chiu V, Vail TP, Rubash HE, Berry DJ (2010) The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res 468:45–51CrossRefGoogle Scholar
  3. 3.
    Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ (2009) The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am 91:128–133CrossRefGoogle Scholar
  4. 4.
    Hossain F, Patel S, Haddad FS (2010) Midterm assessment of causes and results of revision total knee arthroplasty. Clin Orthop Relat Res 468:1221–1228CrossRefGoogle Scholar
  5. 5.
    Kim YH, Park JW, Kim JS, Kim DJ (2015) The outcome of infected total knee arthroplasty: culture-positive versus culture-negative. Arch Orthop Trauma Surg 135:1459–1467CrossRefGoogle Scholar
  6. 6.
    Windisch C, Brodt S, Roehner E, Matziolis G (2017) C-reactive protein course during the first 5 days after total knee arthroplasty cannot predict early prosthetic joint infection. Arch Orthop Trauma Surg 137:1115–1119CrossRefGoogle Scholar
  7. 7.
    Janz V, Wassilew GI, Kribus M, Trampuz A, Perka C (2015) Improved identification of polymicrobial infection in total knee arthroplasty through sonicate fluid cultures. Arch Orthop Trauma Surg 135:1453–1457CrossRefGoogle Scholar
  8. 8.
    Balato G, Franceschini V, Ascione T, Lamberti A, Balboni F, Baldini A (2018) Diagnostic accuracy of synovial fluid, blood markers, and microbiological testing in chronic knee prosthetic infections. Arch Orthop Trauma Surg 138:165–171CrossRefGoogle Scholar
  9. 9.
    Balato G, Franceschini V, Ascione T, Lamberti A, D'Amato M, Ensini A, Baldini A (2017) High performance of α-defensin lateral flow assay (Synovasure) in the diagnosis of chronic knee prosthetic infections. Knee Surg Sports Traumatol Arthrosc 26:1717–1722CrossRefGoogle Scholar
  10. 10.
    Berger P, Van Cauter M, Driesen R, Neyt J, Cornu O, Bellemans J (2017) Diagnosis of prosthetic joint infection with alpha-defensin using a lateral flow device: a multicentre study. Bone Joint J. 99B:1176–1182CrossRefGoogle Scholar
  11. 11.
    Suda AJ, Tinelli M, Beisemann ND, Weil Y, Khoury A, Bischel OE (2017) Diagnosis of periprosthetic joint infection using alpha-defensin test or multiplex-PCR: ideal diagnostic test still not found. Int Orthop 41:1307–1313CrossRefGoogle Scholar
  12. 12.
    Gehrke T, Lausmann C, Citak M, Bonanzinga T, Frommelt L, Zahar A (2018) The accuracy of the alpha defensin lateral flow device for diagnosis of periprosthetic joint infection: comparison with a gold standard. J Bone Joint Surg Am. 100:42–48CrossRefGoogle Scholar
  13. 13.
    Kasparek MF, Kasparek M, Boettner F, Faschingbauer M, Hahne J, Dominkus M (2016) Intraoperative diagnosis of periprosthetic joint infection using a novel alpha defensin lateral flow assay. J Arthroplasty 31:2871–2874CrossRefGoogle Scholar
  14. 14.
    Sigmund IK, Holinka J, Gamper J, Staats K, Böhler C, Kubista B, Windhager R (2017) Qualitative α defensin test (Synovasure) for the diagnosis of periprosthetic infection in revision total joint arthroplasty. Bone Joint J 99B:66–72CrossRefGoogle Scholar
  15. 15.
    Renz N, Yermak K, Perka C, Trampuz A (2018) Alpha defensin lateral flow test for diagnosis of periprosthetic joint infection: not a screening but a confirmatory test. J Bone Joint Surg Am 100:742–750CrossRefGoogle Scholar
  16. 16.
    Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J (2014) Combined measurement of synovial fluid α-defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection. J Bone Joint Surg Am 96:1439–1445CrossRefGoogle Scholar
  17. 17.
    Bonanzinga T, Zahar A, Dütsch M, Lausmann C, Kendoff D, Gehrke T (2017) How reliable is the alpha-defensin immunoassay test for diagnosing periprosthetic joint infection? A prospective study. Clin Orthop Relat Res 475:408–415CrossRefGoogle Scholar
  18. 18.
    Frangiamore SJ, Gajewski ND, Saleh A, Farias-Kovac M, Barsoum WK, Higuera CA (2016) α-Defensin accuracy to diagnose periprosthetic joint infection-best available test? J Arthroplasty 31:456–460CrossRefGoogle Scholar
  19. 19.
    Bingham J, Clarke H, Spangehl M, Schwartz A, Beauchamp C, Goldberg B (2014) The alpha defensin-biomarker assay can be used to evaluate the potentially infected total joint arthroplasty. Clin Orthop Relat Res 472:4006–4009CrossRefGoogle Scholar
  20. 20.
    Shahi A, Parvizi J, Kazarian GS, Higuera C, Frangiamore S, Bingham J, Beauchamp C, Valle CD, Deirmengian C (2016) The alpha-defensin test for periprosthetic joint infections is not affected by prior antibiotic administration. Clin Orthop Relat Res 474:1610–1615CrossRefGoogle Scholar
  21. 21.
    Deirmengian C, Kardos K, Kilmartin P, Gulati S, Citrano P, Booth RE Jr (2015) The alpha-defensin test for periprosthetic joint infection responds to a wide spectrum of organisms. Clin Orthop Relat Res 473:2229–2235CrossRefGoogle Scholar
  22. 22.
    Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Booth RE Jr, Parvizi J (2015) The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip. Clin Orthop Relat Res 473:198–203CrossRefGoogle Scholar
  23. 23.
    Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J (2014) Diagnosing periprosthetic joint infection: has the era of the biomarker arrived? Clin Orthop Relat Res 472:3254–3262CrossRefGoogle Scholar
  24. 24.
    Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N (2018) The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty 33:1309–1314CrossRefGoogle Scholar
  25. 25.
    Suen K, Keeka M, Ailabouni R, Tran P (2018) Synovasure 'quick test' is not as accurate as the laboratory-based α-defensin immunoassay: a systematic review and meta-analysis. Bone Joint J 100B:66–72CrossRefGoogle Scholar
  26. 26.
    Eriksson HK, Nordström J, Gabrysch K, Hailer NP, Lazarinis S (2018) Does the alpha-defensin immunoassay or the lateral flow test have better diagnostic value for periprosthetic joint infection? A systematic review. Clin Orthop Relat Res 476:1065–1072CrossRefGoogle Scholar
  27. 27.
    Ahmad SS, Hirschmann MT, Becker R, Shaker A, Ateschrang A, Keel MJB, Albers CE, Buetikofer L, Maqungo S, Stöckle U, Kohl S (2018) A meta-analysis of synovial biomarkers in periprosthetic joint infection: Synovasure™ is less effective than the ELISA-based alpha-defensin test. Knee Surg Sports Traumatol Arthrosc 26:3039–3047CrossRefGoogle Scholar
  28. 28.
    Di Donato SL, Balato G, Mariconda M, Baldini A (2017) Quantitative vs qualitative assessment of alpha-defensin in periprosthetic joint infection: a systematic review and meta-analysis. PROSPERO CRD42017077276.
  29. 29.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–34CrossRefGoogle Scholar
  30. 30.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRefGoogle Scholar
  31. 31.
    Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58:982–990CrossRefGoogle Scholar
  32. 32.
    Shamseer L, Moher D, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647CrossRefGoogle Scholar
  33. 33.
    Doebler P, Holling H, Böhning D (2012) A mixed model approach to meta-analysis of diagnostic studies with binary test outcome. Psychol Methods 17:418CrossRefGoogle Scholar
  34. 34.
    Ahmad SS, Shaker A, Saffarini M, Chen AF, Hirschmann MT, Kohl S (2016) Accuracy of diagnostic tests for prosthetic joint infection: a systematic review. Knee Surg Sports Traumatol Arthrosc 24:3064–3074CrossRefGoogle Scholar
  35. 35.
    Alijanipour P, Bakhshi H, Parvizi J (2013) Diagnosis of periprosthetic joint infection: the threshold for serological markers. Clin Orthop Relat Res 471:3186–3195CrossRefGoogle Scholar
  36. 36.
    Ascione T, Pagliano P, Balato G, Mariconda M, Rotondo R, Esposito S (2016) Oral therapy, microbiological findings, and comorbidity influence the outcome of prosthetic joint infections undergoing 2-stage exchange. J Arthroplasty 32:2239–2243CrossRefGoogle Scholar
  37. 37.
    Lee YS, Koo KH, Kim HJ, Tian S, Kim TY, Maltenfort MG, Chen AF (2017) Synovial fluid biomarkers for the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 99:2077–2084CrossRefGoogle Scholar
  38. 38.
    Yuan J, Yan Y, Zhang J, Wang B, Feng J (2017) Diagnostic accuracy of alpha-defensin in periprosthetic joint infection: a systematic review and meta-analysis. Int Orthop 41:2447–2455CrossRefGoogle Scholar
  39. 39.
    Akgün D, Müller M, Perka C, Winkler T (2018) The serum level of C-reactive protein alone cannot be used for the diagnosis of prosthetic joint infections, especially in those caused by organisms of low virulence. Bone Joint J 100:1482–1486CrossRefGoogle Scholar
  40. 40.
    Pérez-Prieto D, Portillo ME, Puig-Verdié L et al (2017) C-reactive protein may misdiagnose prosthetic joint infections, particularly chronic and low-grade infections. Int Orthop 41:1315–1319CrossRefGoogle Scholar
  41. 41.
    Zimmerli W, Moser C (2012) Pathogenesis and treatment concepts of orthopaedic biofilm infections. FEMS Immunol Med Microbiol 65:158–168CrossRefGoogle Scholar
  42. 42.
    Okroj KT, Calkins TE, Kayupov E (2018) The alpha-defensin test for diagnosing periprosthetic joint infection in the setting of an adverse local tissue reaction secondary to a failed metal-on-metal bearing or corrosion at the head-neck junction. J Arthroplasty 33:1896–1898CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Giovanni Balato
    • 1
    Email author
  • Vincenzo de Matteo
    • 1
  • Tiziana Ascione
    • 2
  • Sigismondo Luca Di Donato
    • 1
  • Cristiano De Franco
    • 1
  • Francesco Smeraglia
    • 1
  • Andrea Baldini
    • 3
  • Massimo Mariconda
    • 1
  1. 1.Section of Orthopaedic Surgery, Department of Public Health, School of MedicineFederico II UniversityNaplesItaly
  2. 2.Department of Infectious DiseasesD. Cotugno Hospital, AORN Dei ColliNaplesItaly
  3. 3.IFCA InstituteFlorenceItaly

Personalised recommendations