Exosome profile and composite indices reflect immune exhaustion in periodontitis

Abstract

Introduction: Exosomes are small extracellular vesicles that regulate immune responses, inflammation, and tissue homeostasis. While several exosomal molecules have been investigated individually in periodontitis, a functional characterization based on composite indices has not been explored. This study aimed to profile salivary exosomes in periodontitis using four composite indices (Total Cargo, Purity, Biogenesis, and Immune Index) and correlate them with clinically relevant cytokines.

Materials and methods: A cross-sectional analytic study was conducted on periodontital patients. All patients underwent a clinical periodontal examination. Gingival crevicular fluid was collected and analyzed using a 6-plex exosome characterization panel (CD9, CD63, CD81, VLA-4, Syntenin-1, Cytochrome C) and a 4-plex cytokine panel (IL-1β, IL-8, IL-10, IL-17 A). Four exosomal composite indices were calculated, and Spearman correlations were performed between clinical, biochemical, and exosomal variables.

Results: A total of 33 patients with periodontitis were included, of whom 27% were classified as Stages I-II. Amongst other statistical significances (p < 0.05), Cytochrome C showed correlations with 4–6 mm pockets (r = 0.50) and PIRIM (r = 0.42), while 7–8 mm pockets were associated with CD63 (r = 0.49) and Purity Index (r = 0.48), and negatively with the Biogenesis (r = -0.45), and Immune Indices (r = -0.41). IL-1β showed correlations with the Total Cargo (r = 0.49) and Purity Indices (r = 0.48), and negative correlations with the Immune and Biogenesis Indices (r = -0.47 and − 0.50, respectively). CD81 was negatively correlated with periodontal staging, and IL-10 showed an inverse correlation with periodontal grading.

Conclusion: Composite exosomal indices reflect the balance between canonical biogenesis, immune cell-derived vesicles, and cell damage–associated vesicles in periodontitis. The negative association of CD81 and Immune Index with disease severity suggests immune exhaustion, whereas reduced IL-10 supports impaired regulatory control in advanced stages.