Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: Review of the current evidence

Salivary exRNA biomarkers to detect gingivitis and monitor disease regression

“…Eight salivary exRNAs showed significant positive correlation of their expression levels with improving clinical measures (GI, PI) due to the introduced treatment (brushing teeth), thus making them potentially useful in monitoring the current activity of disease and its treatment response. The identified exRNAs are mostly involved in inflammatory response, antimicrobial activity, innate immune response, apoptosis, neutrophil, eosinophil & macrophage chemotaxis, and bone homeostasis, that is consistent with the current literature as periodontal diseases are mostly inflammatory in origin and involved in immune pathways (Ghallab, ) (Table ). Interestingly, only very few of them had been previously reported in different biofluids, but none of them have been identified in human saliva.…”

“…The basis of biomarker research success in periodontology is to develop a diagnostic method that will have a potential to favourably affect clinical decision‐making, patient outcomes and health care providers (Ghallab, ). Periodontal disease is time‐consuming and expensive to treat, thus prevention and early detection constitutes significant health care benefit (Ghallab, ). Thus, it would be desirable to develop biomarkers for early detection and monitoring of periodontal disease and its treatment response (Giannobile et al., ).…”

“…The basis of biomarker research success in periodontology is to develop a diagnostic method that will have a potential to favourably affect clinical decision-making, patient outcomes and health care providers (Ghallab, 2017). Periodontal disease is time-consuming and expensive to treat, thus prevention and early detection constitutes significant health care benefit (Ghallab, 2017 F I G U R E 3 Validation of HTA 2.0 Affymetrix array profiling results by RT-qPCR. A plot presenting the fold changes and 95% confidence interval (CI) for each of 10 salivary exRNA biomarkers on the log base 2 scale for the following periods: baseline-6 weeks, 3 week-6 weeks and baseline-3 weeks F I G U R E 4 Performance of salivary exRNA biomarkers to classify gingivitis from healthy subjects with no periodontal disease (baseline-6 weeks) [4 exRNAs: SPRR1A (m1), lnc-TET3-2:1 (m2), FAM25A (m7), CRCT1 (m10)] (0.91 AUC, 71% sensitivity, 100% specificity)…”

Salivary levels of specialized pro‐resolving lipid mediators as indicators of periodontal health/disease status

“…In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, microbiologic, biochemical, molecular, immunologic, physiologic and cellular analyses (Bartold, 2018). Accordingly, several publications have disclosed the potential to identify and measure panels of biomarkers in saliva for diagnostic applications, discriminating patient stratification models, monitoring the progression of periodontopathogenic processes, as well as for prognosis and personalized treatment (Brinkmann, Zhang, Giannobile, & Wong, 2011;Ebersole, Nagarajan, Akers, & Miller, 2015;Ghallab, 2018;Korte & Kinney, 2016;Nagarajan, Miller, Dawson, Al-Sabbagh, & Ebersole, 2015). In this line, although some studies have suggested a role of anti-inflammatory and proresolving lipid mediators in periodontitis pathogenesis as detected in gingival crevicular fluid (GCF, Tarannum & Faizuddin, 2017), murine models (Carvalho et al, 2009;Lee et al, 2016;Van Dyke et al, 2015), cell cultures (Cianci et al, 2016;Du, Li, & Liu, 2018) and blood samples (Doğan et al, 2015;Hasturk et al, 2006;Wang et al, 2015), nothing is known regarding the salivary levels of these biomarkers and their relationship with the periodontal health/disease status.…”

Diagnostic accuracy of IL1β in saliva: The development of predictive models for estimating the probability of the occurrence of periodontitis in non‐smokers and smokers

“…Ideally, a salivary diagnostic tool would be a non‐invasive, complementary test for the diagnosis and monitoring of periodontal patients (Miller et al, 2010). It could also be very useful for the early detection of periodontitis in epidemiological studies (Ghallab, 2018). However, if the natural progression of periodontitis substantially complicates the identification of biomarkers in gingival crevicular fluid (GCF) (Kinane et al, 2017), it is reasonable to assume that this problem would be even greater in saliva.…”