title: The alpha defensin-1 biomarker assay can be used to evaluate the potentially infected total joint arthroplasty.
abstract: BACKGROUND
  Diagnosing a periprosthetic joint infection (PJI) requires a complex approach using various laboratory and clinical criteria. A novel approach to diagnosing these infections uses synovial fluid biomarkers. Alpha defensin-1 (AD-1) is one such synovial-fluid biomarker. However little is known about the performance of the AD-1 assay in the diagnosis of PJI.
  
  
  OBJECTIVE
  We sought to (1) determine the sensitivity and specificity of the AD-1 assay in a population of patients being evaluated for PJI, using the Musculoskeletal Infection Society (MSIS) criteria as the reference standard, and (2) compare the AD-1 assay with other currently available clinical tests, specifically cell count, culture, erythrocyte sedimentation rate, and C-reactive protein.
  
  
  METHODS
  A retrospective review was performed of all patients undergoing workup for a PJI at our institution from January to June 2013. Sixty-one AD-1 assays were done in 57 patients. The group included 51 patients with 55 painful joints and six patients who underwent aspiration before second-stage reimplantation. Patients were considered to have a PJI if they met the MSIS criteria. We calculated the sensitivity and specificity of the AD-1 synovial fluid assay, and compared it with the sensitivity and specificity of the synovial fluid cell count, culture, erythrocyte sedimentation rate, and C-reactive protein. There were 19 diagnosed infections in the 61 aspirations, with 21 positive and 40 negative AD-1 assays. There were two false positive and no false negatives AD-1 assays.
  
  
  RESULTS
  The sensitivity and specificity for the AD-1 assay were 100% (95% CI, 79%-100%) and 95% (95% CI, 83%-99%), respectively. The sensitivity and specificity of the other tests ranged from 68% to 95% and 66% to 88%, respectively. The AD-1 assay results outperformed the other tests but did not reach statistical significance except for the sensitivity of the erythrocyte sedimentation rate.
  
  
  CONCLUSIONS
  The sensitivity and specificity of the synovial fluid AD-1 assay exceeded the sensitivity and specificity of the other currently available clinical tests evaluated here but did not reach significance. The AD-1 assay offers another test with high sensitivity and specificity for diagnosing a PJI especially in the case where the diagnosis of PJI is uncertain, but larger studies will be needed to determine significance and cost effectiveness.
  
  
  METHODS
  Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopaedics, Mayo Clinic Phoenix, 5777 E Mayo Blvd., Phoenix, AZ, 85054, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bingham
authors.forename: Henry
authors.initials: H
authors.lastname: Clarke
authors.forename: Mark
authors.initials: M
authors.lastname: Spangehl
authors.forename: Adam
authors.initials: A
authors.lastname: Schwartz
authors.forename: Christopher
authors.initials: C
authors.lastname: Beauchamp
authors.forename: Brynn
authors.initials: B
authors.lastname: Goldberg
mesh_terms: D019643:Arthroplasty, Replacement / Q000009:adverse effects* / Q000295:instrumentation; D001431:Bacteriological Techniques; D015415:Biomarkers / Q000032:analysis; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D007595:Joint Prosthesis / Q000009:adverse effects*; D011237:Predictive Value of Tests; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000378:metabolism / Q000382:microbiology; D012189:Retrospective Studies; D013582:Synovial Fluid / Q000737:chemistry*; D023084:alpha-Defensins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D002097:C-Reactive Protein