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Objectives and questions: Periprosthetic joint infection (PJI) is one of the most severe complications following total joint arthroplasty, requiring revision surgery. Differentiating between septic and aseptic implant failure remains challenging, particularly in low-grade infections, where microbiological cultures sometimes yield false-negative results. Complement components such as C3, C5, and C9 may serve as potential biomarkers for improving diagnostic accuracy. This study investigates their presence in periprosthetic synovial membranes to assess their diagnostic potential for distinguishing between PJI and aseptic failure.

Material and methods: Periprosthetic synovial membrane samples were analyzed from patients undergoing knee or hip revision surgery for suspected PJI or aseptic implant failure. Collected patient data included age, number of prior revisions, comorbidities. CRP levels, leukocyte counts and microbiological culture results were measured. Patients were classified as either septic or aseptic according to the Musculoskeletal Infection Society (MSIS) criteria. Immunofluorescence staining was performed using antibodies against C3, C5, and C9. The fluorescence signal was quantified using image analysis software, and statistical comparisons between groups were conducted using the Mann-Whitney U test for non-normally distributed data.

Results: The CRP-values were significantly elevated in the septic cohort, but no changes were observed in leucocyte count. C9 staining was significantly increased in PJI samples compared to aseptic cases, whereas C3 and C5 showed no significant variation between groups. Further analysis of patient characteristics revealed no direct correlation with fluorescence intensity. Additional evaluation of low-grade infections is currently ongoing to evaluate whether complement factors can further aid in distinguishing low-grade PJI from aseptic failure.

Discussion and conclusions: These findings indicate that C9 may serve as a new biomarker for differentiating PJI from aseptic failure, particularly in tissue-based diagnostics. Future studies with larger cohorts and additional analyses of complement system activation are necessary to further validate these results and explore their diagnostic potential.