Diagnostic accuracy of alpha-defensin ELISA and lateral flow assays for periprosthetic joint infection: a systematic review and meta-analysis

Abstract. Background: Alpha-defensin (AD) is a synovial biomarker that can be used in the diagnosis of periprosthetic joint infection (PJI). Two testing modalities are available: the laboratory-based enzyme-linked immunosorbent assay (ELISA) and the point-of-care (POC) lateral flow (LF) assay. Although both assays have been incorporated into modern PJI diagnostic algorithms, their comparative diagnostic accuracy remains incompletely defined. Methods: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Cochrane databases were searched from 1 January 2000 to 1 February 2024. Studies using contemporary PJI definitions were included. Eligible studies evaluated the diagnostic performance (sensitivity and specificity) of AD-ELISA or AD-LF in patients undergoing evaluation for suspected PJI. Pooled sensitivity and specificity were calculated, and subgroup analyses compared AD assays to traditional synovial markers such as leukocyte count (LC) and polymorphonuclear percentage (PMN %). Results: A total of 51 studies met inclusion criteria. Reported sensitivity and specificity varied widely across studies, with median values of 0.86 and 0.97 for AD-ELISA and 0.84 and 0.97 for AD-LF. Pooled estimates, derived from studies reporting confidence intervals, demonstrated a sensitivity and specificity of 87.8 % (95 % CI, 81.2 %–94.3 %) and 97.9 % (95 % CI, 96.5 %–99.2 %) for AD-ELISA and of 81.8 % (95 % CI, 76.0 %–87.5 %) and 97.0 % (95 % CI, 95.9 %–98.2 %) for AD-LF, respectively. Compared with traditional synovial leukocyte count and PMN %, both assays demonstrated comparable or superior specificity, particularly for AD-ELISA. Risk of bias was generally low across included studies. Conclusion: Both AD assays demonstrate high specificity in diagnosing PJI, but AD-ELISA offers superior sensitivity compared to AD-LF and traditional synovial markers. Given variability in the underlying diagnostic criteria for PJI, these results should be interpreted within the context of differing reference standards. These findings support the continued use of AD-ELISA as a valid diagnostic modality.