An salivary cytokine signature could distinguish carious lesions from healthy oral states in a proof-of-concept study, although its ability to differentiate caries from noncarious gingival inflammation was more limited.

In a case-control ancillary study, researchers used data from the ongoing ORASPORT cohort to analyze 65 patients aged 18 to 30 years who had carious lesions, gingival inflammation, or were healthy.

The investigators collected unstimulated whole saliva and used the ultrasensitive electrochemiluminescence multiplex assay (S-PLEX) Proinflammatory Panel 1 to quantify 9 cytokines: interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17, interferon-gamma, and tumor necrosis factor (TNF)-alpha. They assessed assay sensitivity; linearity; reproducibility; matrix effects; and single-, double-, and triple-cytokine combinations for their ability to discriminate carious lesions from healthy controls, gingival inflammation, and the combined control groups. The study was designed to assess group-level inflammatory signatures rather than diagnostic performance according to lesion stage or depth.

The assay demonstrated high sensitivity and reproducibility. All 9 cytokines were detectable in more than 97% of samples, and 8 were detected in all patients. TNF-alpha was the strongest discriminator of carious lesions from healthy controls and the combined healthy and gingival-inflammation group but did not distinguish carious lesions from gingival inflammation. IL-6 was also elevated among patients with carious lesions compared with healthy controls, whereas IL-1 beta alone did not discriminate between the groups.

However, IL-17 plus TNF-alpha produced the highest area under the receiver operating characteristic curve for distinguishing carious lesions from healthy controls. The same combination, however, had modest discrimination in distinguishing carious lesions from gingival inflammation.

Adding a third cytokine did not meaningfully improve discriminatory performance. The IL-17 plus TNF-alpha plus IL-1 beta combination had modest discrimination in distinguishing carious lesions from the combined healthy and gingival-inflammation group. The researchers therefore considered IL-17 in combination with TNF-alpha and/or IL-1 beta to be candidate salivary signatures warranting prospective validation rather than established diagnostic biomarkers.

The findings were limited by the modest sample size, narrow population of young adults, and cross-sectional design, which prevented causal inference and longitudinal assessment. The absence of radiographic examinations may have resulted in undetected proximal or hidden dentinal lesions, while the lack of periodontal probing limited characterization of gingival inflammation. Excluding patients with both caries and gingival inflammation reduced representation of overlapping oral conditions encountered in clinical practice. The researchers could not stratify carious lesions by severity, and the cytokine-combination analysis was exploratory and post hoc, making the findings hypothesis-generating and in need of validation in larger studies.

“Although their clinical utility remains to be established, such biomarkers may ultimately prove valuable,” wrote lead study author Margaux Dubois, of the Laboratoire MICORALIS in the Faculté de Chirurgie Dentaire Odontologie at the Université Côte d’Azur in France, and colleagues.

The study authors declared no conflicts of interest.

Source: BDJ Open