Salivary IgA antibody to malondialdehyde-acetaldehyde associates with mild periodontal pocket depth.

OBJECTIVE: Oxidized epitopes such as malondialdehyde-acetaldehyde (MAA) play a crucial role in the progression of atherosclerosis through activation of the humoral immune response. The exact mechanism of the association between atherosclerosis and periodontal diseases is not fully understood. The aim of the current study is to evaluate the association of oral humoral immune response to oxidized epitopes with parameters of periodontal disease. MATERIALS AND METHODS: The Parogene cohort consist of patients who have undergone coronary angiography due to cardiac symptoms. In this study, 423 patients were randomly selected for an extensive oral examination. Salivary Immunoglobulin A to oxidized epitopes and bacterial antigens was determined by chemiluminescence immunoassay. RESULTS: In a binary logistic regression model adjusted with periodontal disease confounders, periodontal pocket depth (PPD) 4-5 mm associated with salivary IgA antibodies to MAA-LDL (p = 0.034), heat shock protein 60 of Aggregatibacter actinomycetemcomitans (p = 0.045), Porphyromonas gingivalis (p = 0.045), A. actinomycetemcomitans (p = 0.005), P. intermedia (p = 0.020), and total IgA (p = 0.003). CONCLUSIONS: The current study shows the association of salivary IgA to MAA-LDL with PPD 4-5 mm in a cohort of patients with chronic coronary artery disease. Humoral immune cross-reactivation to oxidized epitopes such MAA-LDL could partly explain the link of periodontitis with systemic diseases.

Saliva and serum biomarkers in periodontitis and coronary artery disease.

AIM: Matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS). MATERIALS AND METHODS: The population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non-periodontitis, and ACS versus non-ACS patients were compared. RESULTS: Saliva MMP-8, MMP-9 and MPO provided significant area-under-curve (AUC) values for periodontitis, 0.69 (<0.001), 0.66 (<0.001) and 0.68 (<0.001), respectively. Serum MMP-8, MMP-9 and MPO levels distinguished ACS from non-ACS patients with AUCs of 0.73 (<0.001), 0.58 (0.03) and 0.68 (<0.001), respectively. Periodontitis confounded the use of serum MMP-9 in diagnostics of ACS. Cardiac status complicated the use of saliva TIMP-1 in periodontal diagnostics. Saliva biomarkers could not be used in ACS diagnosis, and serum biomarkers were not useful in diagnosis of periodontitis. CONCLUSIONS: MMP-8, MMP-9, TIMP-1and MPO are valuable biomarkers for both ACS and periodontitis, but the selection of sample material is crucial; serum is suitable for ACS and saliva for periodontal diagnostic aid.

Aggregatibacter actinomycetemcomitans serotypes associate with periodontal and coronary artery disease status.

AIM: We investigated the association between the Aggregatibacter actinomycetemcomitans serotypes, periodontal status and coronary artery disease (CAD). MATERIALS AND METHODS: The study population included 497 patients who underwent coronary angiography, and clinical oral examination. Quantitative polymerase chain reaction assays were designed to identify the serotypes from saliva samples. RESULTS: Aggregatibacter actinomycetemcomitans serotype frequencies were as follows: serotype "c" 35.7%, "b" 28.6%, "a" 26.2%, "e" 7.1%, "d" 2.4% and "f" 0%. The subjects with a detectable serotype had less teeth and higher bleeding on probing than those with no serotype. Serotypes "b" and "c" associated with periodontal probing depths and periodontal inflammatory burden. The saliva and subgingival bacterium quantities and serum antibody levels against A. actinomycetemcomitans were highest in patients harbouring serotype "c." Serotypes "b" and "c" were most frequent (59.3%) in patients with CAD (p = .040), and they associated with the risk of stable CAD with an odds ratio of 2.67 (95% confidence interval 1.06-7.44). Also, the severity of CAD (p = .018) associated with serotypes "b" and "c." CONCLUSIONS: Aggregatibacter actinomycetemcomitans serotypes "b" and "c" associate with both periodontal and CAD status. Detectable serotypes associate with the quantity and the serology of the bacterium emphasizing both local and systemic effect of the A. actinomycetemcomitans serotypes.

Lipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease.

AIM: We aimed to study how lipopolysaccharide (LPS) in saliva and serum associates with each other, periodontal microbial burden, periodontitis and coronary artery disease (CAD). MATERIALS AND METHODS: The used Parogene cohort comprised N = 505 Finnish adults. Coronary diagnosis was acquired by coronary angiography, and the main outcomes were as follows: no significant CAD (n = 123), stable CAD (n = 184) and acute coronary syndrome (n = 169). Periodontitis was defined according to clinical and radiographic examinations. Levels for 75 strains of subgingival bacteria were determined by checkerboard DNA-DNA hybridization. Saliva and serum LPS activity was analysed by Limulus amebocyte lysate assay. RESULTS: The level of 11 bacterial strains, which were mainly oral and respiratory Gram-negative species, associated with salivary LPS levels in an age- and gender-adjusted linear regression. A total of 4.9% of the serum LPS, that is endotoxemia, variation was explainable by saliva LPS among patients with periodontitis (n = 247, R2  = .049, Pearson's r = .222, p < .001). Endotoxemia associated with stable CAD in a confounder adjusted multinomial logistic regression model (OR 1.99, 95% CI 1.04-3.81, p = .039, 3rd tertile). CONCLUSIONS: In particular in periodontitis patients, subgingival microbial burden contributes to endotoxemia. LPS is a possible molecular mediator between periodontitis and CAD.

Genetic variation on the BAT1-NFKBIL1-LTA region of major histocompatibility complex class III associates with periodontitis.

Periodontitis is a chronic inflammatory disease with a multifactorial etiology. We investigated whether human major histocompatibility complex (MHC) polymorphisms (6p21.3) are associated with periodontal parameters. Parogene 1 population samples (n = 169) were analyzed with 13,245 single nucleotide polymorphisms (SNPs) of the MHC region. Eighteen selected SNPs (P ≤ 0.001) were replicated in Parogene 2 population samples (n = 339) and the Health 2000 Survey (n = 1,420). All subjects had a detailed clinical and radiographic oral health examination. Serum lymphotoxin-α (LTA) concentrations were measured in the Parogene populations, and the protein was detected in inflamed periodontal tissue. In the Parogene 1 population, 10 SNPs were associated with periodontal parameters. The strongest associations emerged from the parameters bleeding on probing (BOP) and a probing pocket depth (PPD) of ≥6 mm with the genes BAT1, NFKBIL1, and LTA. Six SNPs, rs11796, rs3130059, rs2239527, rs2071591, rs909253, and rs1041981 (r(2), ≥0.92), constituted a risk haplotype. In the Parogene 1 population, the haplotype had the strongest association with the parameter BOP, a PPD of ≥6 mm, and severe periodontitis with odds ratios (95% confidence intervals) of 2.63 (2.21 to 3.20), 2.90 (2.37 to 3.52), and 3.10 (1.63 to 5.98), respectively. These results were replicated in the other two populations. High serum LTA concentrations in the Parogene population were associated with the periodontitis risk alleles of the LTA SNPs (rs909253 and rs1041981) of the haplotype. In addition, the protein was expressed in inflamed gingival connective tissue. We identified a novel BAT1-NFKBIL1-LTA haplotype as a significant contributor to the risk of periodontitis. The genetic polymorphisms in the MHC class III region may be functionally important in periodontitis susceptibility.

Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis.

AIM: Chronic periodontitis has an episodic and multifactorial character, with fluctuations in bacterial burden, inflammatory response, and tissue destruction. We investigated the association of selected salivary biomarkers with periodontal parameters and validated the use of a novel salivary diagnostic approach, the cumulative risk score (CRS), in detection of periodontitis in subjects with angiographically verified coronary artery disease diagnosis. MATERIALS AND METHODS: The concentrations of matrix metalloproteinase (MMP)-8, interleukin (IL)-1ß, and Porphyromonas gingivalis were analysed from saliva of 493 subjects. The subjects participated in a detailed clinical and radiographic oral examination. The CRS index, combining the three salivary biomarkers, was calculated for each subject. RESULTS: High salivary concentrations of MMP-8, IL-1ß, and P. gingivalis were associated with deepened periodontal pockets and alveolar bone loss, and MMP-8 and IL-1ß with bleeding on probing. The CRS index had a stronger association with moderate to severe periodontitis (OR 6.13; 95% CI 3.11-12.09) than any of the markers alone. CONCLUSIONS: Salivary concentrations of MMP-8, IL-1ß, and P. gingivalis are associated with various clinical and radiographic measures of periodontitis. The CRS index, combining the three salivary biomarkers, is associated with periodontitis more strongly than any of the markers alone regardless of the coronary artery disease status of the patients.

Shotgun metagenomic analysis of the oral microbiome in gingivitis: a nested case-control study.

Background: Gingivitis, i.e. inflammation of the gums, is often induced by dentalplaque. However, its exact link to the oral microbiota remains unclear. Methods: In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined theoral microbiome composition of gingivitis patients and their controlsusing shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33%was considered 'generalized gingivitis/initial periodontitis'(GG/IP), and BOP <33% as 'healthy and localized gingivitis'(H/LG). Functional potential was inferred using HUMANn3. Results: GG/IP exhibited an increase in the abundance of Actinomyces, Porphyromonas, Aggregatibacter, Corynebacterium, Olsenella, and Treponema, whereas H/LG exhibited an increased abundance of Candidatus Nanosynbacter. Nineteen bacterial species and fourmicrobial functional profiles, including L-methionine, glycogen, andinosine-5'-phosphate biosynthesis, were associated with GG/IP. Constructing models with multiple markers resulted in a strong predictive value for GG/IP, with an area under the curve (ROC) of 0.907 (95% CI: 0.848-0.966). Conclusion: We observed distinct differences in the oral microbiome between the GG/IP and H/LG groups, indicating similar yet unique microbial profiles and emphasizing their potential role in progression of periodontal diseases.

Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease.

AIM: We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. MATERIALS AND METHODS: The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays. RESULTS: In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not. CONCLUSIONS: The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.

Self-reported bruxism mirrors anxiety and stress in adults.

OBJECTIVES: The aims were to analyze whether the levels of self-reported bruxism and anxiety associate among otherwise healthy subjects, and to investigate the independent effects of anxiety and stress experience on the probability of self-reported bruxism. STUDY DESIGN: As part of a study on irregular shift work, a questionnaire was mailed to all employees of the Finnish Broadcasting Company with irregular shift work (number of subjects: n=750) and to an equal number of randomly selected employees in the same company with regular eight-hour daytime work. RESULTS: The response rates were 82.3% (56.6 % men) and 34.3 % (46.7 % men), respectively. Among the 874 respondents, those aware of more frequent bruxism reported significantly more severe anxiety (p<0.001). Adjusted by age and gender, frequent bruxers were more than two times more likely to report severe stress (odds ratio 2.5; 95% confidence interval 1.5-4.2) and anxiety (odds ratio 2.2; 95% confidence interval 1.3-3.6) than non-or-mild bruxers. CONCLUSIONS: Present findings suggest that self-reported bruxism and psychological states such as anxiety or stress may be related in working age subjects.

Attenuation of vagal recovery during sleep and reduction of cortisol/melatonin ratio in late afternoon associate with prolonged daytime sleepiness among media workers with irregular shift work.

BACKGROUND: Media work is characterized by information flow, deadlines, and 24/7 alertness. Good recovery prevents stress-related disorders. METHODS: The standardized questionnaire included items about health, health habits, sleep, work conditions, and work stress. Recordings of 24-hr heart rate variability (HRV) and four salivary samples for cortisol and melatonin levels were analyzed from 70 randomly selected workers with irregular shift work, and 70 workers with normal daytime work. RESULTS: Irregular shift work increased the risk of insufficient recovery when compared to normal daytime work (OR 2.0; P < 0.05). In the group of workers with insufficient subjective recovery, HRV was attenuated (P < 0.05) during the early hours of night, and cortisol/melatonin ratio was decreased (P < 0.05) in the afternoon. CONCLUSIONS: Physiological changes underlying subjective feelings of insufficient recovery are measurable. Attenuated HRV during sleep reflects prolonged sympathetic drive and/or impaired parasympathetic recovery. Interactions between cortisol and melatonin hormones might be involved in the development of chronic exhaustion.

Antibody response to oral biofilm is a biomarker for acute coronary syndrome in periodontal disease.

Cumulative evidence over the last decades have supported the role of gum infections as a risk for future major cardiovascular events. The precise mechanism connecting coronary artery disease (CAD) with periodontal findings has remained elusive. Here, we employ next generation phage display mimotope-variation analysis (MVA) to identify the features of dysfunctional immune system that associate CAD with periodontitis. We identify a fine molecular description of the antigenic epitope repertoires of CAD and its most severe form - acute coronary syndrome (ACS) by profiling the antibody reactivity in a patient cohort with invasive heart examination and complete clinical oral assessment. Specifically, we identify a strong immune response to an EBV VP26 epitope mimicking multiple antigens of oral biofilm as a biomarker for the no-CAD group. With a 2-step biomarker test, we stratify subjects with periodontitis from healthy controls (balanced accuracy 84%), and then assess the risk for ACS with sensitivity 71-89% and specificity 67-100%, depending on the oral health status. Our findings highlight the importance of resolving the immune mechanisms related to severe heart conditions such as ACS in the background of oral health. Prospective validation of these findings will support incorporation of these non-invasive biomarkers into clinical practice.

Common complement factor H polymorphisms are linked with periodontitis in elderly patients.

BACKGROUND: In our recent genome-wide association study, we found that genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum matrix metalloproteinase 8 (MMP-8) concentration and the release of MMP-8 from neutrophils. As MMP-8 is centrally involved in the pathogenesis of periodontitis, we aimed to evaluate the presence of genetic polymorphisms of S100A8/A9/A12, MMP8, and CFH in periodontitis. In addition, we studied whether polymorphisms of these genes affect the concentrations of S100A8, S100A12, MMP-8, or complement activation marker in saliva. METHODS: We genotyped four single-nucleotide polymorphisms (SNPs, rs1560833 in S100A8/A9/A12, rs11225395 in MMP8, rs800292 in CFH, and rs1061170 in CFH) and measured salivary concentrations of S100A8, S100A12, MMP-8, and terminal complement complex (TCC) in the Parogene cohort (n = 508). The cohort was composed of patients with an indication to coronary angiography and all underwent a clinical and radiographic oral examination. RESULTS: CFH polymorphisms rs800292 and rs1061170 were associated with periodontal parameters. None of the polymorphisms showed association with salivary proteins. However, salivary concentrations of S100A8, S100A12, MMP-8, and TCC were strongly associated with the number of periodontal pockets and alveolar bone loss. CONCLUSION: Interestingly, genetic variants of CFH, MMP8, and S100A8/A9/A12 gene regions did not affect salivary levels of measured proteins. However, saliva levels of S100A8, S100A12, MMP-8, and TCC, and CFH polymorphisms were associated with clinical and radiographic signs of periodontitis. Our study further supports the observations that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.

Periodontitis is associated with angiographically verified coronary artery disease.

INTRODUCTION: We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography. MATERIAL AND METHODS: Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed. RESULTS: Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p = 0.020) and 5.24 (1.90-14.5, p = 0.014), and more than seven teeth with PPD ≥6 mm with ORs 2.44 (1.01-6.07, p = 0.049) and 2.75 (1.16-6.53, p = 0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p = 0.025). Number of stenosed arteries was linearly associated with ABL (p for trend <0.001), number of missing teeth (p < 0.001), and pockets with probing depth ≥6 mm (p = 0.033). CONCLUSIONS: Compared with patients with no significant stenosis, poor periodontal health including missing teeth, periodontal inflammation, and bone loss is associated with angiographically verified coronary artery narrowing in patients with stable CAD or ACS.

Systemic Antibiotics Influence Periodontal Parameters and Oral Microbiota, But Not Serological Markers.

The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed antibiotics associate with periodontal status, oral microbiota, and antibodies against the periodontal pathogens. The Social Insurance Institution of Finland Data provided the data on the use of systemic antibiotics by record linkage to purchased medications and entitled reimbursements up to 1 year before the oral examination and sampling. Six different classes of antibiotics were considered. The Parogene cohort included 505 subjects undergoing coronary angiography with the mean (SD) age of 63.4 (9.2) years and 65% of males. Subgingival plaque samples were analysed using the checkerboard DNA-DNA hybridisation. Serum and saliva antibody levels to periodontal pathogens were analysed with immunoassays and lipopolysaccharide (LPS) activity with the LAL assay. Systemic antibiotics were prescribed for 261 (51.7%) patients during the preceding year. The mean number of prescriptions among them was 2.13 (range 1-12), and 29.4% of the prescriptions were cephalosporins, 25.7% penicillins, 14.3% quinolones, 12.7% macrolides or lincomycin, 12.0% tetracycline, and 5.8% trimethoprim or sulphonamides. In linear regression models adjusted for age, sex, current smoking, and diabetes, number of antibiotic courses associated significantly with low periodontal inflammation burden index (PIBI, p < 0.001), bleeding on probing (BOP, p = 0.006), and alveolar bone loss (ABL, p = 0.042). Cephalosporins associated with all the parameters. The phyla mainly affected by the antibiotics were Bacteroidetes and Spirochaetes. Their levels were inversely associated with the number of prescriptions (p = 0.010 and p < 0.001) and directly associated with the time since the last prescription (p = 0.019 and p < 0.001). Significant inverse associations were observed between the number of prescriptions and saliva concentrations of Prevotella intermedia, Tannerella forsythia, and Treponema denticola and subgingival bacterial amounts of Porphyromonas gingivalis, P. intermedia, T. forsythia, and T. denticola. Saliva or serum antibody levels did not present an association with the use of antibiotics. Both serum (p = 0.031) and saliva (p = 0.032) LPS activity was lower in patients having any antibiotic course less than 1 month before sampling. Systemic antibiotics have effects on periodontal inflammation and oral microbiota composition, whereas the effects on host immune responses against the periodontal biomarker species seem unchanged.

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.

Smoking confounds the periodontal diagnostics using saliva biomarkers.

BACKGROUND: Smoking is a risk factor for periodontal disease because of its complex impact on the inflammatory response in the periodontium. We investigated the effect of smoking on salivary periodontal biomarkers, matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and myeloperoxidase (MPO). METHODS: Saliva biomarkers were analyzed in the Parogene population (n = 480) comprising a random cohort of patients that have undergone coronary angiography and oral examination. The effect of time since cessation and pack years of smoking on biomarkers were investigated. RESULTS: Saliva MMP-8, MMP-9, TIMP-1, and MPO concentrations distinguished periodontitis patients significantly from patients without periodontitis. When the time since cessation was considered, the area-under-the-curve values (p-value) for periodontitis were 0.76 (<0.001), 0.74 (<0.001), 0.70 (<0.001), and 0.76 (<0.001), respectively. Adding information about smoking habits in the models improved slightly the sensitivities of all biomarkers. In logistic regression model saliva, MMP-8 was mainly affected by pack years of smoking, whereas saliva MMP-9, TIMP-1, and MPO were mostly affected by time since cessation, especially if smoking currently or quit recently (<1 year ago). CONCLUSION: Smoking confounds the salivary diagnostics of periodontitis and should be considered when interpreting the results obtained by potential diagnostic tests.

Saliva and Serum Immune Responses in Apical Periodontitis.

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01-8.33) and 4.91 (2.48-9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48-2.97)), serum IgG to bacterial antigens (4.66 (1.22-10.1)), and Gram-negative subgingival species (1.98 (1.16-3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05-21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis-a putative risk factor for systemic diseases.

Immunologic burden links periodontitis to acute coronary syndrome.

BACKGROUND AND AIMS: Periodontitis, a common polymicrobial inflammatory disease in the tooth supporting tissues, is a risk factor for coronary artery disease. One of the proposed underlying mechanisms is the systemic immune response to periodontal infection. We studied how serum antibodies against seven periodontal pathogens and their subgingival levels associate with each other, periodontitis, and coronary artery disease. METHODS: The Parogene cohort included 505 Finnish patients (mean age 63 y) who underwent coronary angiography, and clinical and radiographic oral examinations. Coronary diagnosis was defined as no significant coronary artery disease (<50% stenosis, n = 152), stable coronary artery disease (≥50% stenosis, n = 184) and acute coronary syndrome (n = 169). Levels of subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum were determined by checkerboard DNA-DNA hybridization. Serum antibody (IgA/IgG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Aggregate IgA/IgG burdens were calculated by summing and standardizing the serum antibody levels. RESULTS: Patients with active periodontitis were characterized by higher levels of subgingival bacteria and corresponding IgA/IgG response. Quartiles 2-4 of serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR 1.84, 95%CI 1.01-3.35 for IgA; OR 1.87, 95%CI 1.01-3.46 for IgG) independently of established cardiovascular risk factors, body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis. CONCLUSIONS: Our findings support the hypothesis that the association between periodontitis and cardiovascular diseases is partly mediated by the immunologic response for periodontal pathogens.

Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype.

Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1ß and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.

Is periodontal infection behind the failure of antibiotics to prevent coronary events?

The use of antimicrobial agents to prevent coronary events is under debate. They have reduced cardiovascular events in some studies, but in others, their effect has not been distinguishable from that of placebo. In addition to Chlamydophila (Chlamydia) pneumoniae as a target pathogen, very few other microbes or infections have been targeted, although an association for instance between cardiovascular disease and periodontitis has been established. In our recent pilot study, long-term clarithromycin treatment reduces recurrent cardiovascular events in subjects without periodontitis, but in subjects with periodontitis, fails to show any effect. As a background infection, periodontitis may overpower the beneficial effects of antibiotics. This paper presents the hypothesis that periodontitis is behind the failure of antibiotics to prevent coronary events. We discuss the systemic effects of periodontal infection and consider studies to test our hypothesis, which offers a novel viewpoint for discussion of antibiotics in coronary-disease prevention.