Synovial Myeloperoxidase: Another Biomarker or a Novel Addition in the Quest for Accurate and Timely PJI Diagnosis?

Periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) has well-known consequences of increased morbidity, mortality, and economic burden, and has been found to occur in <2% of primary TJAs1,2. With increasingly innovative technology, advances in artificial intelligence, and increased research focus, synovial and serum biomarkers have gained attention and advanced to the point of inclusion in recent PJI diagnostic criteria3,4. However, the diagnostic criteria continue to evolve, and new biomarkers continue to emerge that may improve the accuracy and cost-effectiveness of diagnosing PJI. Enter myeloperoxidase (MPO) and the study by Ikeda et al. Similar to other biomarkers utilized for PJI diagnosis, such as alpha-defensin and leukocyte esterase, MPO is released by immune cells in response to pathogens. One point of excitement around MPO specifically is its release during the neutrophil extracellular trap (NET) response to pathogens, which could result in MPO identifying PJI earlier than other methods. For this reason, the potential use of MPO in distinguishing PJI from aseptic revision has become prominent in recent years. However, studies validating its use have primarily utilized enzyme-linked immunosorbent assay (ELISA) tests, which are not point-of-care tests (POCTs)5–7. Ikeda et al. have moved this conversation forward through their study of an MPO POCT for diagnosing PJI. The authors utilized prospectively obtained synovial fluid aspirates and compared the results of the MPO POCT, MPO ELISA, and alpha-defensin ELISA tests. To strengthen the validity of the study, they used one of the major PJI diagnostic criteria, the 2nd International Consensus Meeting on Musculoskeletal Infection criteria4, as the standard for defining PJI. With that said, while the study was powered statistically, the sample size of only 46 patients certainly limits this to a true pilot study—as the authors state—and the findings require further validation with far larger sample sizes. The results showed that the MPO POCT performed very well, with 100% sensitivity and 91% specificity, clearly achieving the goal of the pilot stage. Unsurprisingly, given the similar physiological roles of MPO and alpha-defensin, the MPO ELISA results correlated strongly with the alpha-defensin ELISA results. However, the alpha-defensin POCT (lateral flow test) was not utilized. It would be very informative to directly compare the performance between the 2 POCTs in order to determine if this new test is equivalent or superior to the alpha-defensin lateral flow test, and it is likely that this will be the focus of larger studies moving forward. Ikeda et al. also refer to the cost of using alpha-defensin as a biomarker for PJI diagnosis. While the ELISA and lateral flow tests may be relatively expensive, these tests are U.S. Food and Drug Administration (FDA)-approved for use in diagnosing PJI. The leukocyte esterase strip test is relatively inexpensive in comparison. The authors describe the MPO POCT that was utilized but do not state whether it is FDA-approved for this use or mention the cost of this commercially available test, presumably because they are in the process of developing a version that is specifically for PJI diagnosis. Cost comparisons may be more appropriate once this MPO POCT achieves the aforementioned milestones of regulatory approval, commercial availability, and large-scale validation; however, the push for additional and potentially more cost-effective tests is valuable, particularly if they can be utilized interchangeably in diagnostic algorithms, as opposed to being additive tests. Thus, while questions remain regarding the scalability of the results, cost-effectiveness, and advancement over current tests, the study by Ikeda et al. on the use of an MPO POCT for PJI diagnosis is very promising. Given the pilot nature of this study, further work is clearly needed, but, as the multiple versions of PJI diagnostic criteria continue to evolve and grow, time will tell if MPO as a POCT has a role alongside alpha-defensin and leukocyte esterase—or even in place of them.