Abstract
Aseptic prosthetic loosening and periprosthetic joint infections (PJI) are among the most frequent complications after total knee/hip joint arthroplasty (TJA). Current research efforts focus on understanding the involvement of the immune system in these frequent complications. Different immune cell types have already been implicated in aseptic prosthetic loosening and PJI. The aim of this study was to systematically analyze aspirates from knee and hip joints, evaluating the qualitative and quantitative composition of soluble immunoregulatory markers, with a focus on co-inhibitory and co-stimulatory markers. It has been shown that these molecules play important roles in immune regulation in cancer and chronic infectious diseases, but they have not been investigated in the context of joint replacement. For this purpose, aspirates from control joints (i.e., native joints without implanted prostheses), joints with TJA (no signs of infection or aseptic loosening), joints with aseptic implant failure (AIF; i.e., aseptic loosening), and joints with PJI were collected. Fourteen soluble immunoregulatory markers were assessed using bead-based multiplex assays. In this study, it could be shown that the concentrations of the analyzed immunoregulatory molecules vary between control, TJA, AIF, and PJI joints. Comparing TJA patients to CO patients, sCD80 was significantly elevated. The marker sBTLA was significantly elevated in AIF joints compared to TJA joints. In addition, a significant difference for eight markers could be shown when comparing the AIF and CO groups (sCD27, sCTLA-4, sCD137, sCD80, sCD28, sTIM-3, sPD-1, sBTLA). A significant difference was also reached for nine soluble markers when the PJI and CO groups were compared (sLAG-3, sCTLA-4, sCD27, sCD80, sCD28, sTIM-3, sPD-1, IDO, sBTLA). In summary, the analyzed immunoregulatory markers could be useful for diagnostic purposes as well as to develop new therapeutic approaches for AIF and PJI.
Highlights
In recent years, the continuously aging population and associated age-related morbidity have led to a marked increase in the number of implanted joint endoprostheses [1,2,3]
An increase in consequent complications has been observed [2]. These primarily include aseptic prosthetic loosening (referred to in this study as aseptic implant failure (AIF)) and peri-implant fractures, and prosthetic joint infections (PJI), which can lead to septic prosthetic loosening [4,5,6]
Concentrations of 14 immunoregulatory markers in hip and knee joint aspirates in each of the four groups are expressed as mean ± standard deviation
Summary
The continuously aging population and associated age-related morbidity have led to a marked increase in the number of implanted joint endoprostheses [1,2,3]. An increase in consequent complications has been observed [2]. These primarily include aseptic prosthetic loosening (referred to in this study as aseptic implant failure (AIF)) and peri-implant fractures, and prosthetic joint infections (PJI), which can lead to septic prosthetic loosening [4,5,6]. These typical complications can lead to significant limitations in daily activities due to pain, immobility, and chronic infections [7]. As important mediators of osteolysis, macrophages play a significant role in the former complication [5, 8]
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