Analytical and clinical considerations of synovial fluid calprotectin in diagnosing periprosthetic joint infections

Calprotectin is a protein predominantly found in the cytosol of myeloid cells, such as neutrophils and monocytes. Calprotectin has several functions in innate immunity, such as attenuating bacteria, recruiting and activating immune cells, and aiding in the production of pro-inflammatory cytokines and reactive oxygen species. Due to its presence in inflammatory sites, it has been investigated as a biomarker for various medical conditions, especially Inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), and has gained interest in the diagnosis of several infectious diseases, in particular for diagnosing periprosthetic joint infections (PJI). Synovial fluid calprotectin has demonstrated to be a sensitive and specific biomarker for both confirming as well as excluding PJI. Synovial fluid calprotectin can be measured using enzyme-linked immunosorbent assay (ELISA), immunoturbidimetry, and lateral flow methods. It is a generally stable biomarker, showing no significant decrease or increase in its levels despite blood or lipid contamination, storage duration, freeze-thaw cycles, and enzymatic pretreatments for viscosity reduction. This review discusses the biology and physiology of calprotectin, pathophysiology of PJI, and the clinical and analytical considerations surrounding its use in diagnosing PJI.