-Defensin Conventional Markers of Inflammation in Periprosthetic Joint Infection: a Retrospective Study

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2024 Nov 22

PMID 39575176

Authors

Javier Fernandez-Torres

Yessica Zamudio-Cuevas

Karina Martinez-Flores

Ambar Lopez-Macay

Graciela Rosas-Alquicira

Maria Guadalupe Martinez-Zavaleta

Luis Esau Lopez-Jacome

Rafael Franco-Cendejas

Ernesto Roldan-Valadez

Affiliations

Soon will be listed here.

Abstract

Background: Diagnosing periprosthetic joint infection (PJI) remains a significant challenge for healthcare professionals. Commonly utilized inflammatory markers include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cells (WBC). Human -defensin 1 (-defensin) is an antimicrobial peptide elevated in infection, yet its diagnostic value for PJI has not been explored. The purpose of this study was to evaluate the efficacy of synovial -defensin as a diagnostic marker for PJI and to compare its performance with ESR, serum CRP, and WBC.

Methods: We conducted a single-center retrospective study from October 2022 to June 2023. A total of 105 joint fluid samples from revision patients at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra were collected intraoperatively (71 hips, 34 knees) and frozen. According to MSIS criteria, 64 patients were defined as positive for PJI and the remaining 41 were negative. Synovial -defensin levels were quantified using ELISA, serum CRP levels by immunoturbidimetry, and blood ESR and WBC were analyzed. Sensitivity and specificity were determined using ROC curves, and diagnostic performance was compared using the area under the curve (AUC). Cut-off values for diagnosing PJI were established.

Results: Levels of synovial -defensin, ESR, serum CRP, and WBC were significantly higher in the PJI group compared to the non-PJI ( < 0.0001). The AUCs were 0.948 for -defensin, 0.884 for ESR, 0.902 for CRP, and 0.767 for WBC, with a combined AUC of 0.994. Sensitivity/specificity for -defensin, ESR, CRP, and WBC were 0.966/0.830, 0.887/0.791, 0.930/0.771, and 0.820/0.682, respectively. Optimal predictive cut-off values were 1105.8 pg/mL for -defensin, 11.5 mm/h for ESR, 5.55 mg/L for CRP, and 7.3 × 10/mm for WBC.

Conclusion: The synovial -defensin assay demonstrated greater sensitivity and specificity for the diagnosis of PJI compared to ESR, serum CRP and WBC. Therefore, -defensin shows promise as a diagnostic marker for PJI. Simultaneous determination of all markers may increase diagnostic confidence.

References

Masters T, Bhagwate A, Dehankar M, Greenwood-Quaintance K, Abdel M, Mandrekar J . Human transcriptomic response to periprosthetic joint infection. Gene. 2022; 825:146400. PMC: 9007914. DOI: 10.1016/j.gene.2022.146400. View

Ghanem E, Antoci Jr V, Pulido L, Joshi A, Hozack W, Parvizi J . 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. 2009; 13(6):e444-9. DOI: 10.1016/j.ijid.2009.02.017. View

Zhai Y, Feng Y, Ma X, Ma F . Defensins: defenders of human reproductive health. Hum Reprod Update. 2022; 29(1):126-154. PMC: 9825273. DOI: 10.1093/humupd/dmac032. View

Nelson S, Pinkney J, Chen A, Tande A . Periprosthetic Joint Infection: Current Clinical Challenges. Clin Infect Dis. 2023; 77(7):e34-e45. PMC: 11004930. DOI: 10.1093/cid/ciad360. View

Premkumar A, Kolin D, Farley K, Wilson J, McLawhorn A, Cross M . Projected Economic Burden of Periprosthetic Joint Infection of the Hip and Knee in the United States. J Arthroplasty. 2021; 36(5):1484-1489.e3. DOI: 10.1016/j.arth.2020.12.005. View

Banke I, Stade N, Prodinger P, Tubel J, Hapfelmeier A, von Eisenhart-Rothe R . Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers. Eur J Med Res. 2020; 25(1):33. PMC: 7429885. DOI: 10.1186/s40001-020-00434-1. View

Samael Olascoaga-Del A, Sanchez-Evangelista G, Carmona-Navarrete I, Galicia-Sanchez M, Gomez-Luna A, Islas-Arrollo S . [Péptidos antimicrobianos, una alternativa prometedora para el tratamiento de enfermedades infecciosas]. Gac Med Mex. 2018; 154(6):681-688. DOI: 10.24875/GMM.18003445. View

Jordan R, Smith N, Saithna A, Sprowson A, Foguet P . Sensitivities, specificities, and predictive values of microbiological culture techniques for the diagnosis of prosthetic joint infection. Biomed Res Int. 2014; 2014:180416. PMC: 4055545. DOI: 10.1155/2014/180416. View

Parvizi J, Zmistowski B, Berbari E, Bauer T, Springer B, Della Valle C . New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011; 469(11):2992-4. PMC: 3183178. DOI: 10.1007/s11999-011-2102-9. View

10.

Berberich C, Josse J, Ruiz P . Patients at a high risk of PJI: Can we reduce the incidence of infection using dual antibiotic-loaded bone cement?. Arthroplasty. 2022; 4(1):41. PMC: 9450350. DOI: 10.1186/s42836-022-00142-7. View

11.

Yang D, Biragyn A, Hoover D, Lubkowski J, Oppenheim J . Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004; 22:181-215. DOI: 10.1146/annurev.immunol.22.012703.104603. View

12.

Li Z, Zhang Q, Shi L, Gao F, Sun W, Li Z . Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis. Biomed Res Int. 2020; 2020:3704285. PMC: 7688361. DOI: 10.1155/2020/3704285. View

13.

Linke S, Thurmer A, Bienger K, Kleber C, Bellova P, Lutzner J . Microbiological pathogen analysis in native versus periprosthetic joint infections: a retrospective study. J Orthop Surg Res. 2022; 17(1):9. PMC: 8734295. DOI: 10.1186/s13018-021-02850-3. View

14.

Bingham J, Clarke H, Spangehl M, Schwartz A, Beauchamp C, Goldberg B . The alpha defensin-1 biomarker assay can be used to evaluate the potentially infected total joint arthroplasty. Clin Orthop Relat Res. 2014; 472(12):4006-9. PMC: 4397781. DOI: 10.1007/s11999-014-3900-7. View

15.

Bozic K, Kurtz S, Lau E, Ong K, Chiu V, Vail T . The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2009; 468(1):45-51. PMC: 2795838. DOI: 10.1007/s11999-009-0945-0. View

16.

Frangiamore S, Gajewski N, Saleh A, Farias-Kovac M, Barsoum W, Higuera C . α-Defensin Accuracy to Diagnose Periprosthetic Joint Infection-Best Available Test?. J Arthroplasty. 2015; 31(2):456-60. DOI: 10.1016/j.arth.2015.09.035. View

17.

Williams J, Norman P, Stockley I . The value of hip aspiration versus tissue biopsy in diagnosing infection before exchange hip arthroplasty surgery. J Arthroplasty. 2004; 19(5):582-6. DOI: 10.1016/j.arth.2003.11.011. View

18.

Trampuz A, Piper K, Jacobson M, Hanssen A, Unni K, Osmon D . Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007; 357(7):654-63. DOI: 10.1056/NEJMoa061588. View

19.

Tetreault M, Wetters N, Moric M, Gross C, Della Valle C . Is synovial C-reactive protein a useful marker for periprosthetic joint infection?. Clin Orthop Relat Res. 2014; 472(12):3997-4003. PMC: 4397770. DOI: 10.1007/s11999-014-3828-y. View

20.

Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J . Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?. Clin Orthop Relat Res. 2014; 472(11):3254-62. PMC: 4182392. DOI: 10.1007/s11999-014-3543-8. View