Gingival tissue transcriptomes identify distinct periodontitis phenotypes

Abstract

The currently recognized principal forms of periodontitis-chronic and aggressive-lack an unequivocal, pathobiology-based foundation. We explored whether gingival tissue transcriptomes can serve as the basis for an alternative classification of periodontitis. We used cross-sectional whole-genome gene expression data from 241 gingival tissue biopsies obtained from sites with periodontal pathology in 120 systemically healthy nonsmokers with periodontitis, with available data on clinical periodontal status, subgingival microbial profiles, and serum IgG antibodies to periodontal microbiota. Adjusted model-based clustering of transcriptomic data using finite mixtures generated two distinct clusters of patients that did not align with the current classification of chronic and aggressive periodontitis. Differential expression profiles primarily related to cell proliferation in cluster 1 and to lymphocyte activation and unfolded protein responses in cluster 2. Patients in the two clusters did not differ with respect to age but presented with distinct phenotypes (statistically significantly different whole-mouth clinical measures of extent/severity, subgingival microbial burden by several species, and selected serum antibody responses). Patients in cluster 2 showed more extensive/severe disease and were more often male. The findings suggest that distinct gene expression signatures in pathologic gingival tissues translate into phenotypic differences and can provide a basis for a novel classification.

Keywords: classification; cluster analysis; diagnosis; gene expression; genomics; periodontal diseases.

Figure 1.

Comparison of cluster assignment. Transcriptomic profile-based cluster assignments of study participants are compared with the current primary classification of periodontitis—chronic (CP) or aggressive (AgP)—as well as with an extent-based subdivision based on the 1999 “International Workshop” criteria (localized or generalized periodontitis). The degree of concordance among the alternative ways of classifying periodontitis was assessed via the Herbert-Arabie adjusted Rand index. Perfect alignment is indicated by an adjusted Rand index of 1; random alignment by an adjusted Rand index of 0.