Salivary proteotypes of gingivitis tolerance and resilience

Bostancı, Nagihan; Silbereisen, Angelika; Bao, Kai; Grossmann, Jonas; Nanni, Paolo; Fernández, Claudia Nélida; Nascimento, Gustavo G.; Belibasakis, Georgios N.; López, Rodrigo

doi:10.1111/jcpe.13358

Cited by 15 publications

(16 citation statements)

References 48 publications

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“…It is known from the literature that MMP-8 and MMP-9 have similar specificity to degrade matrix, and they have the same inhibitors (e.g. TIMP-1) 3 , 20 – 22 . When comparing the gingivitis vs health groups, the values of the above biomarker relations were of the same order as the values of the single biomarkers.…”

Section: Resultsmentioning

confidence: 99%

“…To validate a subset of existing candidate protein markers that are most relevant for periodontal disease, we performed ELISA-based analysis in a cross-sectional cohort, using saliva as a diagnostic biological fluid. During the past years, emerging protein detection technologies have revealed a large number of candidate periodontitis biomarkers 3 , 20 . Unfortunately, there exists a big gap between biomarker discovery and validation due to several factors 23 .…”

Section: Discussionmentioning

confidence: 99%

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Validation and verification of predictive salivary biomarkers for oral health

Bostancı

Mitsakakis

Afacan

et al. 2021

Sci Rep

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Oral health is important not only due to the diseases emerging in the oral cavity but also due to the direct relation to systemic health. Thus, early and accurate characterization of the oral health status is of utmost importance. There are several salivary biomarkers as candidates for gingivitis and periodontitis, which are major oral health threats, affecting the gums. These need to be verified and validated for their potential use as differentiators of health, gingivitis and periodontitis status, before they are translated to chair-side for diagnostics and personalized monitoring. We aimed to measure 10 candidates using high sensitivity ELISAs in a well-controlled cohort of 127 individuals from three groups: periodontitis (60), gingivitis (31) and healthy (36). The statistical approaches included univariate statistical tests, receiver operating characteristic curves (ROC) with the corresponding Area Under the Curve (AUC) and Classification and Regression Tree (CART) analysis. The main outcomes were that the combination of multiple biomarker assays, rather than the use of single ones, can offer a predictive accuracy of > 90% for gingivitis versus health groups; and 100% for periodontitis versus health and periodontitis versus gingivitis groups. Furthermore, ratios of biomarkers MMP-8, MMP-9 and TIMP-1 were also proven to be powerful differentiating values compared to the single biomarkers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Validation and verification of predictive salivary biomarkers for oral health

Bostancı

Mitsakakis

Afacan

et al. 2021

Sci Rep

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“…The magnitude and consistency of immune-inflammatory response are controlled at a number of regulatory, genetic and epigenetic levels that likely influence the individual variability in the severity and rate of progression of the disease. Consistently, experimental gingivitis studies have revealed that the intensity of the gingival inflammation in periodontitis-susceptible patients is strictly related to the individual inflammatory host response rather than being entirely due to differences in the amount and composition of the bacterial biofilm [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 90%

Gingival Crevicular Fluid Cytokines in Moderate and Deep Sites of Stage III Periodontitis Patients in Different Rates of Clinical Progression

et al. 2020

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Clinical criteria are inappropriate to measure the degree of susceptibility to progression of periodontal damage. Thus, the aim of this study was to assess whether gingival crevicular fluid (GCF) levels of cytokines could discriminate patients suffering from stage III periodontitis with moderate (Grade B) and rapid rates of progression (Grade C) prior to and 6 months after non-surgical periodontal treatment. GCF samples were obtained from moderate and deep sites of 20 patients diagnosed as Grade B and 20 patients as grade C stage III periodontitis and analyzed for interleukin (IL)-1β, IL-9, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) using a high-sensitivity Bio-Plex Suspension Array System. At baseline, higher IL-1β but lower IL-9 GCF levels were observed in moderate sites of the grade C compared to the grade B group. In spite of comparable clinical improvement, this difference maintained after treatment, suggesting a residual pro-inflammatory state. In deep sites, no differences were observed between periodontitis groups except for VEGF levels that decreased more in Grade B periodontitis at 6 months post-therapy. A mathematical model was constructed to identify Grade C periodontitis patients based on the subjects’ GCF levels of IL-1β and IL-9, which achieved an area under the receiver-operating characteristic (ROC) curve of 0.94. This study can contribute to the early assessment of risk of future breakdown in periodontitis patients.

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“…However, the composition of the oral or tooth-specific microbiome may not be exclusively associated with the maintenance of oral health or disease [ 16 ]. It has been shown that patients who abstain from oral hygiene procedures subsequently develop different responses to their accumulated plaque [ 13 , 17 , 18 ]. These different clinical responses enabled a classification into “periodontal-resistant” and “periodontal-insufficient” or ”high responder” and “low responder”, respectively [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that patients who abstain from oral hygiene procedures subsequently develop different responses to their accumulated plaque [ 13 , 17 , 18 ]. These different clinical responses enabled a classification into “periodontal-resistant” and “periodontal-insufficient” or ”high responder” and “low responder”, respectively [ 18 ]. Hence, the host’s response to pathogenic stimuli also accounts for the maintenance of oral health or development of disease.…”

Section: Introductionmentioning

confidence: 99%

Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring

Paqué

Herz

Wiedemeier

et al. 2021

JPM

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This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.

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Salivary proteotypes of gingivitis tolerance and resilience

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 15 publications

References 48 publications

Validation and verification of predictive salivary biomarkers for oral health

Validation and verification of predictive salivary biomarkers for oral health

Gingival Crevicular Fluid Cytokines in Moderate and Deep Sites of Stage III Periodontitis Patients in Different Rates of Clinical Progression

Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring

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