Artikel
PD-1/PD-L1 signaling in periprosthetic joint infections (PJI) of the knee
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Autoren
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Arne Kienzle
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
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Denise Jahn
- Charité Universitätsmedizin Berlin, Julius Wolff Institut, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
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Renqiu Qiao
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
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Clemens Gwinner
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
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Weijie Du
- Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charité, Berlin, Germany
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Dimitrios Laurin Wagner
- Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charité, Berlin, Germany
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Serafeim Tsitsilonis
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
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Carsten Perka
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
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Georg Duda
- Charité Universitätsmedizin Berlin, Julius Wolff Institut, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
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Yi Ren
- Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité University Hospital Berlin, Berlin, Germany
| Veröffentlicht: | 21. Oktober 2024 |
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Gliederung
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Objectives: In our prior research, we identified enhanced osteoclastogenesis as a primary factor compromising bone structure in periprosthetic joint infection (PJI), which can potentially lead to implant failure through aseptic loosening. To date, the mechanisms driving this excessive osteoclastogenesis remain unclear. In this study, we explore the hypothesis that selective local and systemic upregulation of PD-1/PD-L1 contributes to the observed overshooting osteoclastogenesis.
Methods: Peripheral blood, bone, and bone marrow of 65 patients (20 primary osteoarthritis, 21 PJI septic explantation, 24 PJI prosthesis reimplantation) were analyzed for their bone microstructure and cell composition. Immunocytochemistry, flow cytometry, bone resorption assay, and ELISA were performed using cell cultured samples of five specimens per group.
Results and conclusion: PD-1 positive monocytes (peripheral blood: control: 48.0% vs PJI: 96.8%, p<0.001; bone marrow specimens: control: 20.1% vs PJI: 55.7%, p=0.003) and sPD-L1 levels (0.003 vs 0.014 ng/mL, p=0.001) were significantly elevated in PJI. PD-L1 stimulation enhanced osteoclast formation and function (extracellular TRAP activity in PJI 3.781 mU/mL vs 1.995 mU/mL in control, p<0.001), while PD-1 inhibitor nivolumab reversed these effects (3.781 mU/mL in PJI vs 1.976 mU/mL after nivolumab, p<0.001). Pit formation assay demonstrated increased osteoclast bone matrix resorption after treatment with PD-L1 in PJI (8.86% control vs 23.5% PJI, p=0.001). Impact of PD-1 and nivolumab was significantly more pronounced in PJI compared to the control.
Our study suggests PD-1/PD-L1 signaling plays a significant role in PJI, particularly contributing to overshooting osteoclastogenesis. These findings highlight the potential of PD-1 inhibitors as a novel approach to manage this challenging clinical condition.
