C9 immunostaining as a tissue biomarker for periprosthetic joint infection diagnosis.

Background: Culture-negative periprosthetic joint infections (PJI) are often false diagnosed as aseptic implant failure leading to unnecessary revision surgeries due to repeated infections. A marker to increase the security of e PJI diagnosis is therefore of great importance. The aim of this study was to test C9 immunostaining of periprosthetic tissue as a novel tissue-biomarker for a more reliable identification of PJI, as well as potential cross-reactivity. Method: We included 98 patients in this study undergoing septic or aseptic revision surgeries. Standard microbiological diagnosis was performed in all cases for classification of patients. Serum parameters including C-reactive protein (CRP) serum levels and white blood cell (WBC) count were included, and the periprosthetic tissue was immunostained for C9 presence. The amount of C9 tissue staining was evaluated in septic versus aseptic tissue and the amount of C9 staining was correlated with the different pathogens causing the infection. To exclude cross-reactions between C9 immunostaining and other inflammatory joint conditions, we included tissue samples of a separate cohort with rheumatoid arthritis, wear particles and chondrocalcinosis. Results: The microbiological diagnosis detected PJI in 58 patients; the remaining 40 patients were classified as aseptic. Serum CRP values were significantly increased in the PJI cohort. Serum WBC was not different between septic and aseptic cases. We found a significant increase in C9 immunostaining in the PJI periprosthetic tissue. To test the predictive value of C9 as biomarker for PJI we performed a ROC analyses. According to the Youden's criteria C9 is a very good biomarker for PJI detection with a sensitivity of 89% and a specificity of 75% and an AUC of 0.84. We did not observe a correlation of C9 staining with the pathogen causing the PJI. However, we observed a cross reactivity with the inflammatory joint disease like rheumatoid arthritis and different metal wear types. In addition, we did not observe a cross reactivity with chondrocalcinosis. Conclusion: Our study identifies C9 as a potential tissue-biomarker for the identification of PJI using immunohistological staining of tissue biopsies. The use of C9 staining could help to reduce the number of false negative diagnoses of PJI.

The terminal complement pathway is activated in septic but not in aseptic shoulder revision arthroplasties.

BACKGROUND: The early diagnosis of suspected periprosthetic low-grade infections in shoulder arthroplasties is important for the outcome of the revision surgical procedures. The aim of this study was to investigate new biomarkers of infection in revision shoulder arthroplasties, taking into account the implant design, patient age, and comorbidities. METHODS: The study included 33 patients with shoulder arthroplasties undergoing revision surgical procedures. Microbiological diagnostic testing was performed in all cases. C-reactive protein serum levels and white blood cell counts were evaluated, and the periprosthetic tissue was stained immunohistologically for the terminal complement pathway components (C3, C5, and C9) and for CD68 and α-defensin. RESULTS: Microbiological diagnostic testing detected a periprosthetic infection in 10 reverse shoulder arthroplasties and in 4 anatomic shoulder arthroplasties, while the remaining 19 shoulder arthroplasties were classified as aseptic. We observed more Staphylococcus epidermidis infections in reverse shoulder arthroplasties and more Staphylococcus aureus infections in anatomic shoulder arthroplasties. The revision rate correlated with pre-existing comorbidities and number of previous surgical procedures. The C-reactive protein values and the incidence of specific periprosthetic radiolucent lines were significantly increased in septic revision cases. We found increased staining for all tested complement factors (C3, C5, and C9) but not for α-defensin and CD68 in septic tissue. The most interesting finding was that C9 separated septic from aseptic tissue with a predictive specificity of 100% and a sensitivity of 88.89%. CONCLUSION: We observed a strong correlation between C9 expressions in septic revision tissue. We propose that the terminal complement pathway, especially C9 deposition, may be a potential biomarker to identify septic complications using tissue biopsy specimens.