gms | German Medical Science

Objectives: Treatment of periprosthetic joint infections (PJIs) is based upon pathogen identification via microbiological culture. Empirical antimicrobial therapy is applied in culture-negative PJI. Treatment success is monitored via routine blood tests (CRP, leukocyte count) and clinical presentation. The patient's immune response is neither monitored nor considered in the therapeutic decision-making process. We developed a quantitative high-throughput immunoproteomic infection array (IA), to investigate individual pathogen-specific antibody responses during PJI treatment.

Methods: A prospective matched cohort pilot study to investigate patients' acute and long-term antibody production during two-stage septic revision arthroplasty was performed, with patients undergoing aseptic revision arthroplasty as controls. The IA is a state-of-the-art custom bead-based suspension array (Luminex^®-based) for simultaneous measurement of antibody specificities directed against 30 different PJI-pathogens (Table 1 [Tab. 1]). IA was prepared by cultivating and purifying extracellular proteins of the 30 pathogens, and coupling these proteins to MagPlex beads with unique spectral signatures. Antibody binding was measured on a BioPlex^® 200 system, and analyzed using a dedicated app (xMAPr). Nine PJI patients undergoing revision arthroplasty of the hip (THA, n=7) or knee (TKA, n=2) between 06/2020 and 06/2021 were matched to 10 controls (THA, n=8; TKA, n=2). Standardized samples (periprosthetic soft tissue, synovial fluid) were collected intraoperatively from all participants. For IA, a total of 461 samples (233 serum, 228 EDTA) were taken at standardized time points until final follow-up.

Results and conclusion: IA delivered reliable results and was able to trace the dynamics of the humoral immune response to PJI against PJI-pathogens in all patients (Figure 1 [Fig. 1]). A longitudinal decline in pathogen-specific antibody production was found in all PJI patients, which correlated with clinically successful treatment. Microbiological cultures identified a pathogen in 4 septic cases, while 5 cases remained culture-negative. IA was able to detect a pathogen-specific antibody response in 5 of 9 septic cases. Microbiological culture results and IA were concordant in 2 cases (S. epidermidis, n=2). All microbiological cultures of the aseptic control group remained negative. IA data were concordant with these microbiological cultures, except for one aseptic patient, where IA detected antibodies directed at a single pathogen (C. striatum).

Our proof-of-principle study demonstrates that IA allows for a quantification and monitoring of individual immune responses to PJI and PJI-treatment. The clinical significance of IA must be further investigated.