Immune checkpoint upregulation in periprosthetic joint infection. Issue 11 (5th February 2022) - Warren, Shay I.
Abstract: Periprosthetic joint infections (PJI) induce an immunosuppressive cytokine profile through an unknown mechanism. Immune checkpoints, like programmed cell death 1 (PD‐1) and its ligand (PD‐L1), initiate innate immunosuppressive pathways essential for self‐tolerance. Several malignancies and chronic infections co‐opt these pathways to derive a survival advantage. This study evaluates PD‐1/PD‐L1 expression in periprosthetic tissue from patients undergoing revision hip or knee arthroplasty for a PJI versus an aseptic failure. PD‐1/PD‐L1 in the global tissue sample and the high‐power microscopic field of maximum expression was analyzed prospectively using immunohistochemistry. Fifteen patients with a PJI (45%) and 16 patients with an aseptic failure (52%) were included. PD‐1 expression was uniformly low. Maximum PD‐L1 expression was upregulated in patients with a PJI (25%, interquartile range [IQR]: 5%–75%) versus an aseptic failure, (8%, IQR: 1%–48%, p = 0.039). In the PJI cohort, maximum PD‐L1 expression was higher among patients who developed a recurrent PJI (68%, IQR: 53%–86% vs. 15%, IQR: 5%–70%, p = 0.039). Patients with global PD‐L1 over 5% trended toward a near 22‐fold increase in the odds of reinfection (odds ratio [OR]: 21.9, 95% confidence interval [CI]: 0.9–523.5, p = 0.057) and patients with maximum PD‐L1 over 20% trended toward a 15‐fold increase in the odds of reinfection (OR: 15.0, 95% CI: 0.6–348.9, p = 0.092). These results support immune checkpoint upregulation as a mechanism of PJI‐induced local immune dysfunction. Future studies should confirm PD‐L1 as a risk factor for reinfection in larger cohorts.