Rapid Alpha-Defensin Test Demonstrates a High Level of Accuracy in Diagnosing PJI
In a study published online ahead of print by The Journal of Bone & Joint Surgery, the new alpha-defensin lateral flow test – authorized for marketing by the US Food & Drug Administration (FDA) last year – showed a high level of sensitivity and specificity in diagnosing periprosthetic joint infection (PJI) in total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients.
The data presented in the study were instrumental in the FDA’s authorization of the test, which is the first rapid test specifically designed and validated to aid in the diagnosis of PJI. The alpha-defensin test also represents the first diagnostic test specifically designed for use in orthopaedics.
Alpha defensins are peptides produced by the immune system specifically in response to an infection. The new alpha-defensin lateral flow test, which provides results in 10 to 20 minutes, measures alpha-defensin levels in samples of synovial fluid from the affected joint. An alpha-defensin enzyme-linked immunosorbent assay (ELISA) is also available, providing results in 24 to 48 hours.
For this study, the researchers used synovial fluid samples from 305 TKA (n= 203) and THA (n=102) patients to evaluate the accuracy of the alpha-defensin lateral flow test in distinguishing between patients with and without PJI. The study cohort included 57 patients who had been diagnosed with a PJI based on expert review.
The alpha-defensin lateral flow test demonstrated high sensitivity and specificity: 94.3% and 94.5%, respectively, when excluding rare poor-quality synovial fluid samples composed of substantial blood (greater than 1M RBCs/μL). Including even the poor-quality samples, the test had a sensitivity of 89.5% and specificity of 94.8%.
Another important finding was that the diagnostic performance of the rapid lateral flow assay matched the accuracy of the laboratory-based test for alpha-defensin. The diagnostic performance of both tests closely matched the standard approach to PJI diagnosis, based on a combination of clinical findings and laboratory tests (Musculoskeletal Infection Society criteria).
The authors said that, “Our study enhances the literature by extending the evaluation of alpha defensin to a formal diagnostic trial, thus confirming the solid diagnostic performance demonstrated by previous studies using other methods.” They emphasized the need for further studies to compare different approaches to diagnosis in patients with suspected PJI.
Disclosures: This study was sponsored by Zimmer Biomet, manufacturer of the Synovasure alpha-defensin lateral flow and ELISA tests. Carl Deirmengian, MD, is a paid consultant and paid presenter or speaker for and receives research support from Zimmer Biomet. He is the founder of CD Diagnostics, which was acquired by Zimmer Biomet in 2016. John Madigan, MD, and Sujith Kallur Mallikarjuna, MSRS, MIM, are employees of Zimmer Biomet. Janet Conway, MD, is a paid consultant for and receives other financial or material support from Zimmer Biomet. Dr. Conway receives research support from CD Diagnostics. Carlos Highera, MD, receives research support from CD Diagnostics and Zimmer Biomet. Robin Patel, MD, receives research support from CD Diagnostics.
Deirmengian C, Madigan J, Kallur Mallikarjuna S, Conway J, Higuera C, Patel R. Validation of the alpha defensin lateral flow test for periprosthetic joint infection. J Bone Joint Surg Am. 2020 Nov 5. doi: 10.2106/JBJS.20.00749. Online ahead of print.