Comparative Analysis of Immune Cell-Type Abundances in Periprosthetic Tissues Across Arthroplasty Failure Etiologies

BACKGROUND: Although cellularity is traditionally evaluated morphologically, an emerging transcriptome-sequencing-based algorithm enables simultaneous inference of cellular information. We studied whether cellularity profiles predicted using CIBERSORTx would (1) depict immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies, and (2) provide prognostic value for identifying cases of periprosthetic joint infection (PJI). METHODS: CIBERSORTx-derived cellularity profiles were evaluated in 185 periprosthetic tissue samples, including 135 from patients with PJI (64 males; median age, 66 years) and 50 from those with aseptic failure (AF) (36 males; median age, 62.5 years), that had been subjected to bulk RNA sequencing. Kaplan-Meier survival analysis was performed to assess prognostic outcomes in PJI. RESULTS: Of the 22 evaluated cell types, 5 were significantly elevated in PJI cases: plasma cells, resting memory CD4+ T cells, CD8+ T cells, activated mast cells, and M1 macrophages (all p < 0.05 after Benjamini-Hochberg [BH] correction). Conversely, 3 cell types were significantly elevated in AF cases: gamma delta T cells, M0 macrophages, and M2 macrophages (all p < 0.05 after BH correction). Of the combined immune cell populations, total B cells, total T cells, and natural killer cells were significantly elevated in PJI cases, while total macrophages/monocytes were significantly elevated in AF cases (all p < 0.05 after BH correction). Patients with PJI who had a CD8+/regulatory T cell (Treg) ratio above the median had a significantly lower rate of infection recurrence than those below the median (log-rank p = 0.0252). CONCLUSIONS: CIBERSORTx analysis of samples from periprosthetic tissues predicted distinct immune cell profiles that differed between PJI and aseptic arthroplasty failure modes, and also identified a high CD8+/Treg ratio as a potential prognostic marker. This transcriptomic approach provides a novel, single-assay strategy for evaluating local immune cell responses across arthroplasty failure etiologies. CLINICAL RELEVANCE: The comparative analysis of immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies revealed distinct immune microenvironment signatures that differentiate PJI from AF. Additionally, the finding that a higher CD8+/Treg cell ratio is associated with a lower rate of infection recurrence offers a potential prognostic marker to help identify patients with PJI who are at a lower risk for treatment failure.