Abstract

Periodontitis is the most prevalent inflammatory disease of the periodontium, and is related to oral and systemic health. Exosomes are emerging as non-invasive biomarker for liquid biopsy. We here evaluated the levels of programmed death-ligand 1 (PD-L1) mRNA in salivary exosomes from patients with periodontitis and non-periodontitis controls. The purposes of this study were to establish a procedure for isolation and detection of mRNA in exosomes from saliva of periodontitis patients, to characterize the level of salivary exosomal PD-L1, and to illustrate its clinical relevance. Bioinformatics analysis suggested that periodontitis was associated with an inflammation gene expression signature, that PD-L1 expression positively correlated with inflammation in periodontitis based on gene set enrichment analysis (GSEA) and that PD-L1 expression was remarkably elevated in periodontitis patients versus control subjects. Exosomal RNAs were successfully isolated from saliva of 61 patients and 30 controls and were subjected to qRT-PCR. Levels of PD-L1 mRNA in salivary exosomes were higher in periodontitis patients than controls (P < 0.01). Salivary exosomal PD-L1 mRNA showed significant difference between the stages of periodontitis. In summary, the protocols for isolating and detecting exosomal RNA from saliva of periodontitis patients were, for the first time, characterized. The current study suggests that assay of exosomes-based PD-L1 mRNA in saliva has potential to distinguish periodontitis from the healthy, and the levels correlate with the severity/stage of periodontitis.

Highlights

  • Periodontitis is one of the most prevalent disease in dentistry, impairing the integrity of the periodontium and leading to tooth loss

  • Given the association of periodontitis with inflammation, and the importance of Programmed death-ligand 1 (PD-L1) in inflammatory immunity, we analyzed database to test whether periodontitis correlates with pocket depth (PD)-L1

  • gene set enrichment analysis (GSEA) analysis revealed that periodontitis is positively associated with an inflammation signature, and PD-L1 is positively correlated with an inflammation signature in periodontitis (Figure 1A)

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Summary

Introduction

Periodontitis is one of the most prevalent disease in dentistry, impairing the integrity of the periodontium and leading to tooth loss. Periodontitis is a chronic inflammatory disease caused by microorganisms colonizing the dentogingival interface (Slots, 2013). The diagnosis of periodontitis was mostly based on clinical and radiographic evaluations without specific evaluation of the underlying inflammatory response (Buduneli and Kinane, 2011; Baeza et al, 2016). Programmed death-ligand 1 (PD-L1), known as the B7-H1 receptor, plays an important role in cell-mediated immune responses (Gianchecchi et al, 2013). High expression of PD-L1 in host cells may contribute to the chronicity of inflammatory disorders (Zamani et al, 2016)

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