Search

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10 -4 ), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10 -5 ) and RNASE2 (rs2771342, P = 2.84×10 -5 ) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10 -14 ) and HLA-DPA1 (rs17214512, P = 5.14×10 -5 ). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.

Generalized aggressive periodontitis (GAgP) presents a reduced response to non-surgical therapy. However, it is not clear if the initial clinical, microbiological or immunological characteristics are impacting the worse response to treatment. This study aimed to identify the predictive value of clinical, microbiological and immunological patterns on the clinical response to therapy in GAgP patients. Twenty-four GAgP patients were selected, and gingival crevicular fluid (GCF) and subgingival biofilm were collected. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia levels were evaluated by qPCR, and IL-1β and IL-10 concentration by ELISA. Twelve patients were treated with SRP (scaling and root planning), and twelve with SRP plus 375 mg amoxicillin and 250 mg metronidazole (8/8 hours, 7 days) (SRP + AM). The clinical changes (Probing Pocket Depth [PPD] reduction and Clinical Attachment Level [CAL] gain) 6 months post-treatment were correlated to the initial clinical, inflammatory and microbiological variables using stepwise logistic regression (α = 5%). CAL gain at 6 months was 1.16 ± 0.77 for SRP and 1.74 ± 0.57 mm for SRP + AM (P > .05). PPD reduction was 1.96 ± 0.82 for SRP and 2.45 ± 0.77 mm for SRP + AM (P < .05). In the SRP group, IL-10 showed a predictive value for clinical response. The higher the IL-10 concentration at baseline, the higher the reduction in PPD at 6 months (P = .01, r = .68). However, when antimicrobials were administered, no significant influence was detected (P > .05). It can be concluded that the IL-10 levels in GFC act as a predictor of clinical response to GAgP. Moreover, the intake of antimicrobials appears to overlap the influence of the inflammatory response on clinical response to treatment. Clinical trial registration number: NCT03933501., (© 2019 The Scandinavian Foundation for Immunology.)

To investigate in datasets of immunologic parameters from early-onset and late-onset periodontitis patients (EOP and LOP), the existence of hidden random fluctuations (anomalies or noise), which may be the source for increased frequencies and longer periods of exacerbation, resulting in rapid progression in EOP. Principal component analysis (PCA) was applied on a dataset of 28 immunologic parameters and serum IgG titers against periodontal pathogens derived from 68 EOP and 43 LOP patients. After excluding the PCA parameters that explain the majority of variance in the datasets, i.e. the overall aberrant immune function, the remaining parameters of the residual subspace were analyzed by computing their sample entropy to detect possible anomalies. The performance of entropy anomaly detection was tested by using unsupervised clustering based on a log-likelihood distance yielding parameters with anomalies. An aggregate local outlier factor score (LOF) was used for a supervised classification of EOP and LOP. Entropy values on data for neutrophil chemotaxis, CD4, CD8, CD20 counts and serum IgG titer against Aggregatibacter actinomycetemcomitans indicated the existence of possible anomalies. Unsupervised clustering confirmed that the above parameters are possible sources of anomalies. LOF presented 94% sensitivity and 83% specificity in identifying EOP (87% sensitivity and 83% specificity in 10-fold cross-validation). Any generalization of the result should be performed with caution due to a relatively high false positive rate (17%). Random fluctuations in immunologic parameters from a sample of EOP and LOP patients were detected, suggesting that their existence may cause more frequently periods of disease activity, where the aberrant immune response in EOP patients result in the phenotype "rapid progression"., Competing Interests: The authors have declared that no competing interests exist.

Aggregatibacter actinomycetemcomitans (Aa) is a low-abundance Gram-negative oral pathobiont that is highly associated with a silent but aggressive orphan disease that results in periodontitis and tooth loss in adolescents of African heritage. For the most part Aa conducts its business by utilizing strategies allowing it to conceal itself below the radar of the host mucosal immune defense system. A great deal of misinformation has been conveyed with respect to Aa biology in health and disease. The purpose of this review is to present misconceptions about Aa and the strategies that it uses to colonize, survive, and evade the host. In the process Aa manages to undermine host mucosal defenses and contribute to disease initiation. This review will present clinical observational, molecular, and interventional studies that illustrate genetic, phenotypic, and biogeographical tactics that have been recently clarified and demonstrate how Aa survives and suppresses host mucosal defenses to take part in disease pathogenesis. At one point in time Aa was considered to be the causative agent of Localized Aggressive Periodontitis. Currently, it is most accurate to look at Aa as a community activist and necessary partner of a pathogenic consortium that suppresses the initial host response so as to encourage overgrowth of its partners. The data for Aa's activist role stems from molecular genetic studies complemented by experimental animal investigations that demonstrate how Aa establishes a habitat (housing), nutritional sustenance in that habitat (food), and biogeographical mobilization and/or relocation from its initial habitat (transportation). In this manner Aa can transfer to a protected but vulnerable domain (pocket or sulcus) where its community activism is most useful. Aa 's "strategy" includes obtaining housing, food, and transportation at no cost to its partners challenging the economic theory that "there ain't no such thing as a free lunch." This "strategy" illustrates how co-evolution can promote Aa's survival, on one hand, and overgrowth of community members, on the other, which can result in local host dysbiosis and susceptibility to infection.

Aim: It has been suggested that periodontitis may be associated with increased oxidative stress. The objective of this study is to evaluate the possible differences in antioxidant status between chronic periodontitis (CP) and aggressive periodontitis (AP), by assessing the concentrations of antioxidants with total antioxi-dant status (TAS) and lipid peroxidation status in serum and gingival crevicular fluid (GCF) of these patients., Materials and Methods: Forty-six patients with CP, 32 patients with AP, and 50 healthy controls were included in this study. The level of enzymatic antioxidant, superoxide dismutase (SOD), nonenzymatic antioxidant uric acid, and TAS with lipid peroxidation measured in serum and GCF of patients suffering from CP and AP were compared with the healthy controls., Results: The TAS is decreased and malondialdehyde (MDA) level is increased in both serum and GCF in CP and AP compared with healthy controls (p < 0.001). Superoxide dismutase activities in GCF and serum are found to be low in both the groups of periodontitis (p < 0.001). The uric acid levels are found to be inconsistent in GCF and serum in both the groups of periodontitis., Conclusion: Lipid peroxidation and TAS were affected at systemic level in serum and in GCF of the periodontal pockets, in CP and AP. Similar comments may be made for the decrease in SOD activities and inconsistent uric acid levels., Clinical Significance: Increased oxidative stress may have a role in the pathogenesis of periodontal disease activity.

Objective: Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP., Methods: We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias., Results: Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51)., Conclusion: This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.