Related Experiment Video
Updated: Aug 5, 2026

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction
Published on: December 3, 2017
Complement factors C3 and C5 as tissue biomarkers for differentiating periprosthetic joint infection from aseptic
Jasmin Damm1, Christoph H Lohmann1, Sebastian Illiger1
11Department of Orthopaedics, Otto von Guericke University Magdeburg, Germany.
Background:
The diagnosis of periprosthetic joint infection (PJI), and particularly low-grade ((LG) PJI) infections, remains a clinical challenge. Systemic inflammatory markers sometimes yield false-negative results in inapparent cases, complicating the differentiation from aseptic loosening (AL). This exploratory study evaluated tissue-based complement factors C3 and C5 as biomarkers compared to terminal factor C9 and established systemic parameters.
Methods:
Fifty-five patients undergoing revision arthroplasty were categorized into high-grade PJI (HG) PJI, N = 20), (LG) PJI (N = 14), and AL (N = 21). Serum parameters (C-reactive protein (CRP), white blood cells (WBC)) were analyzed by immunohistochemistry for tissue-based C3, C5, and C9. Diagnostic performance was assessed via ROC analysis.
Results:
Pathogen spectra differed significantly, with (LG) PJI dominated by Cutibacterium acnes and (HG) PJI by staphylococci. ROC analysis showed that serum CRP accurately identified (HG) -PJI, but failed in (LG) PJI. WBC demonstrated limited accuracy. In contrast, C3 detection in tissues exhibited superior performance, particularly for identifying (LG) PJI versus (HG) PJI. C5 detection remained robust in both PJI types. Terminal factor C9 yielded lower overall discrimination and significant cross-reactivity in AL cases.
Conclusions:
Central complement factors C3 and C5 serve as robust tissue biomarkers for PJI, outperforming C9 and systemic parameters. Their implementation may improve clinical decision-making, especially in (LG) PJI cases, where standard diagnostic criteria remain inconclusive.
Insights
Tissue complement factors C3 and C5 show promise as superior biomarkers for diagnosing periprosthetic joint infections (PJI), especially low-grade PJI, outperforming systemic markers.
Area of Science:
- Orthopedic Surgery
- Immunology
- Biomarker Discovery
Background:
- Diagnosing periprosthetic joint infection (PJI), particularly low-grade PJI, is challenging.
- Systemic inflammatory markers can be unreliable, leading to misdiagnosis compared to aseptic loosening (AL).
- Novel tissue-based biomarkers are needed for accurate PJI diagnosis.
Purpose of the Study:
- To evaluate tissue-based complement factors C3 and C5 as diagnostic biomarkers for PJI.
- To compare their performance against terminal factor C9 and established systemic markers (CRP, WBC).
- To assess diagnostic accuracy in differentiating high-grade PJI (HG PJI), low-grade PJI (LG PJI), and AL.
Main Methods:
- Retrospective analysis of 55 patients undergoing revision arthroplasty (HG PJI, LG PJI, AL).
- Immunohistochemical analysis of tissue for complement factors C3, C5, and C9.
- ROC analysis to assess the diagnostic performance of tissue markers versus serum CRP and WBC.
Main Results:
- Pathogen spectra differed: LG PJI by Cutibacterium acnes, HG PJI by staphylococci.
- Serum CRP accurately identified HG PJI but failed in LG PJI; WBC showed limited accuracy.
- Tissue C3 demonstrated superior performance for LG PJI vs. HG PJI; C5 was robust in both PJI types.
- Tissue C9 showed lower discrimination and cross-reactivity with AL.
Conclusions:
- Tissue-based complement factors C3 and C5 are robust biomarkers for PJI diagnosis.
- These tissue markers outperform C9 and systemic parameters, particularly for LG PJI.
- Implementing C3 and C5 may enhance clinical decision-making in challenging PJI cases.

