Investigation of the pathogen-specific antibody response in periprosthetic joint infection.

PURPOSE: Periprosthetic joint infections (PJIs) are a very demanding complication of arthroplasty. Diagnosis of PJI and pathogen identification pose considerable challenges in clinical practice. We hypothesized that the pathogen-specific immune response to PJI reflects the infection process, provides clinically relevant information on disease course, and has the potential to further optimize antimicrobial therapy. METHODS: We conducted a prospective matched cohort pilot study with 13 patients undergoing two-stage septic revision arthroplasty (PJI patients) between 06/2020 and 06/2021, as well as 11 control patients undergoing one-stage aseptic revision arthroplasty (Non-PJI patients). Pre-, intra- and postoperative serum samples were collected at standardized time points. We developed a custom Luminex®-based quantitative bead-based suspension array (Infection Array; IA), and used it for simultaneous measurement of antibody specificities against 32 pathogens commonly associated with PJI in 267 serum samples. RESULTS: The IA was able to trace the dynamics of the pathogen-specific humoral immune response in all patients against PJI-related pathogens, prominently coagulase-negative staphylococci and streptococci. Pathogen-specific serum antibody titers declined in 62% of PJI patients over the course of treatment, while no changes in antibody titers were observed in 82% of Non-PJI patients during this study. Our serological data strongly suggested that antibody signatures reflect an immune response to microbial invasion. CONCLUSION: Our results provide insights into the pathophysiology of PJI and information on the individual disease courses. The IA is therefore a promising and novel serological tool of high resolution for monitoring the immunoproteomic footprints of infectious pathogens in the course of PJI.

Platelets, Bacterial Adhesins and the Pneumococcus.

Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and activation of the clotting system. Bacterial proteins leading to platelet activation and aggregation have been identified, and while platelet receptors are recognized, induced signal transduction cascades are still often unknown. In addition to proteinaceous adhesins, pathogenic bacteria such as Staphylococcus aureus and Streptococcus pneumoniae also produce toxins such as pneumolysin and alpha-hemolysin. They bind to cellular receptors or form pores, which can result in disturbance of physiological functions of platelets. Here, we discuss the bacteria-platelet interplay in the context of adhesin-receptor interactions and platelet-activating bacterial proteins, with a main emphasis on S. aureus and S. pneumoniae. More importantly, we summarize recent findings of how S. aureus toxins and the pore-forming toxin pneumolysin of S. pneumoniae interfere with platelet function. Finally, the relevance of platelet dysfunction due to killing by toxins and potential treatment interventions protecting platelets against cell death are summarized.