Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis.

The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual's risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25-22.0), IgG burden (3.79, 1.78-8.08), LPS (2.19, 1.38-3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10-18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.

Subgingival bacterial burden in relation to clinical and radiographic periodontal parameters.

BACKGROUND: This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota. METHODS: Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes. RESULTS: All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P <0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ≥ 6 mm, BOP, and ABL, except Aggregatibacter actinomycetemcomitans. Levels of Gram-negative oral bacteria correlated significantly with those of Gram-positive species (r = 0.840, P <0.001). In multiple logistic regression analysis, the prevalence of the etiologic bacterial group, levels of Gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, whereas other bacterial complexes and levels of Gram-positive species did not. CONCLUSIONS: Although levels of Gram-negative and -positive species paralleled periodontal parameters, only the species considered etiologic were associated with ABL.

Single nucleotide polymorphism -799C/T in matrix metalloproteinase-8 promoter region in arterial disease.

Arterial disease is associated with elevated serum matrix metalloproteinase (MMP)-8 concentration. We studied the role of two promoter region single nucleotide polymorphisms (SNPs) of MMP-8 gene in the arterial disease. The population comprised patients with arterial disease (n = 124) and healthy blood donors (n = 100) as a reference group for MMP-8 SNPs (-799C/T and -381A/G) genotypes and serum concentrations. Genotype frequencies for MMP-8 -799C/T SNP in arterial disease were C/C (43.5%), C/T (32.3%) and T/T (24.2%), and in the reference group they were C/C (50.0%), C/T (40.0%) and T/T (10.0%; P = 0.012). The -799C allele frequency was lower in the patients (59.7%) than in the reference group (70.0%; P = 0.023). The -799C allele showed protective effects against the arterial disease with an odds ratio [95% confidence interval (CI)] of 0.372 (0.141-0.980, P = 0.045) after adjustment for age, gender, and serum MMP-8 and TIMP-1 concentrations. Only in the reference group and whole study population (n = 224), the -799TT genotype significantly associated with an increase in serum MMP-8 concentrations (P = 0.047, 0.025). The -799C allele appeared protective against the arterial disease. The genotype may have an effect on systemic MMP-8 levels which could not, however, be seen in the arterial disease patients probably as a result of the strong inflammation involved in the disease pathogenesis.

Salivary MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis.

AIM: Salivary matrix metalloproteinase (MMP)-8 and -14, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were analysed aiming to detect potential markers of advanced periodontitis in saliva. In addition, we compared two MMP-8 detection methods, a time-resolved immunofluorometric assay (IFMA) and an enzyme-linked immunoassay (ELISA), to differentiate periodontitis subjects from controls. MATERIAL AND METHODS: Concentrations of MMP-8, MMP-14, TIMP-1, and ICTP were analysed from salivary specimens of 165 subjects, including 84 subjects having at least 14 teeth with periodontal pocket (pocket depth > or =4 mm) and 81 subjects without pocket depth as their controls. RESULTS: Salivary MMP-8 detection by IFMA differentiated periodontitis subjects from controls more strongly than by ELISA. Salivary MMP-8, TIMP-1, and ICTP concentrations were higher in periodontitis subjects than those in controls. When only smokers were included in the analysis these differences were lost. The MMP-8/TIMP-1 ratio and the combination of MMP-8 and ICTP differentiated periodontitis and control groups even in smoker subjects. CONCLUSION: Salivary MMP-8, TIMP-1, ICTP, and especially their ratios and combinations are potential candidates in the detection of advanced periodontitis. Differentiating periodontitis and control subjects with salivary MMP-8 detection is dependent on the selected techniques.

Plasma level of tissue inhibitor of matrix metalloproteinase-1 but not that of matrix metalloproteinase-8 predicts survival in head and neck squamous cell cancer.

Expression of matrix metalloproteinase-8 (MMP-8) in tongue cancer cells has been associated with an improved prognosis. MMP-8 is inhibited by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and elevated levels of TIMP-1 in blood have been associated with poor prognosis in many cancers. We wished to evaluate the usefulness of peripheral blood MMP-8 and TIMP-1 levels as well as the genotypes of MMP8 and TIMP1 in predicting prognosis in head and neck squamous cell carcinoma (HNSCC). Plasma concentrations of MMP-8 and TIMP-1 were analyzed in 136 HNSCC patients. MMP8 and TIMP1 genotypes were determined by analysis of single nucleotide polymorphisms (SNP) in peripheral blood DNA. The mean follow-up time was 3.3years. We found that plasma MMP-8 level did not predict survival but that TIMP-1 level was associated with survival. The adjusted hazard ratio of death scored as a continuous variable on the log(10) scale was 23.2 (95% CI 1.88-286, P=0.01) and that of MMP-8 1.24 (95% CI 0.54-2.84, P=0.61). Immunohistochemical staining showed that TIMP-1 was expressed in vascular endothelium of tumor. TIMP-1 levels were associated with TIMP1 genotype in women but not in men. MMP8 genotype did not correlate with survival or MMP-8 level. Plasma TIMP-1 levels predict survival in HNSCC. TIMP-1 expression is genetically controlled in women. As TIMP-1 inhibits the activity of MMP-8 and it also functions as a growth factor, it may directly influence HNSCC progression.