T- and B-cell subsets in periodontitis.

A large amount of information is available, in the medical literature, on the molecular and immunological mechanisms in which T- and B-cells are involved in the pathogenesis of inflammatory diseases. This review attempts to describe the most important features of the T-cell subsets and their cytokine networks in periodontitis, including the interaction of pathogens with different cell subsets and their gene-expression profiles. Additionally, the known interactions of T- and B-cell subsets in periodontitis are described. The purpose of this article was to provide an overview of the cell interactions and cytokine networks specifically involved in the pathogenesis of periodontitis, and models and paradigms from recent research in this area are presented. However, the review of the literature also revealed that relatively little is known about the genetic or structural factors that confer cross-reactivity of natural and/or autoreactive antibodies in the immunopathogenesis of periodontitis. Pathogens, in turn, are continuously evolving and creating mechanisms to evade immunological reactions controlled and modulated by T- and B-cells.

B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis.

The up-regulation of the B7-H1 receptors in host cells might influence the chronicity of inflammatory disorders that frequently precede the development of human cancers. B7-H1 expression has been detected in the majority of human cancers, leading to anergy and apoptosis of activated T cells, and enabling tumor cells to overcome host response. Porphyromonas gingivalis (P. gingivalis), a putative periodontal pathogen, is an etiologic agent of periodontitis and expresses a variety of virulence factors. In this study, the expression of B7-H1 and B7-DC receptors on squamous cell carcinoma cells SCC-25 and BHY and primary human gingival keratinocytes (PHGK) was analyzed after infection with two virulent P. gingivalis strains in vitro. After 48h, the cells were stained with antibodies for human B7-H1 and B7-DC and further analyzed by flow cytometry. RNA was extracted and gene expression of B7-H1 or B7-DC was quantified by real time PCR. After infection with P. gingivalis, both B7-H1 and B7-DC receptors were up-regulated. The mean fluorescence intensity (MFI) increased from 4.5 to 9.9 (B7-H1) and from 6.9 to 15.0 (B7-DC) (p<0.05, respectively) in SCC-25 cells. PHGK showed an increase from 4.8 to 12.4 (B7-H1) and from 5.5 to 15.6 (B7-DC) (p<0.05, respectively). Streptococcus salivarius K12, a commensal bacterium, caused no up-regulation. After 24h, the expression of B7H1 and B7-DC mRNA in infected cells, normalized to GAPDH and in relation to non-infected cells, was 6.4 fold (B7-H1) and 8.6 fold (B7-DC) higher. In PHGK B7-H1/DC mRNA expression increased 8.2 fold (B7-H1) and 5.9 fold (B7DC) (p<0.05) respectively. The results of the study demonstrate that in contrast to S. salivarius K12 virulent P. gingivalis strains are able to induce the expression of the B7-H1 and B7-DC receptors in squamous carcinoma cells and human gingival keratinocytes, which might facilitate immune evasion by oral cancers.

A novel approach to the use of subgingival controlled-release chlorhexidine delivery in chronic periodontitis: a randomized clinical trial.

BACKGROUND: We aimed to analyze clinical, microbiologic, and serologic effects of chlorhexidine (CHX) chips used as a subgingival controlled-release delivery device before and immediately after scaling and root planing (SRP). METHODS: Twenty-four patients presenting with ≥12 teeth with probing depth (PD) ≥5 mm and bleeding on probing were assigned in test or control groups. After prophylaxis, CHX chips (test) or placebo chips (control) were placed in pockets with PD ≥5 mm. Ten days later, SRP was performed in all teeth with PD ≥4 mm in a single appointment. Immediately after SRP, new chips were inserted in all pockets with PD ≥5 mm. Parameters were assessed at baseline; beginning of SRP; and 1, 3, and 6 months after treatment. Subgingival samples were obtained at baseline; beginning of SRP; and at 1 month after treatment. Periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola were analyzed. Serum levels of high sensitive C-reactive and lipopolysaccharide-binding proteins were measured. The changes of the parameters between and within the groups were tested by Mann-Whitney U test (P <0.05). RESULTS: All clinical and serologic parameters improved in both groups over time. There was a significant difference in clinical attachment level (CAL) gain from baseline to 6 months between groups (1.17 mm in the test group versus 0.79 mm in the placebo group) (P <0.05). The treatment with CHX chips showed a greater reduction of the microorganisms of the "red complex" after 1 month (P = 0.02). CONCLUSION: The use of CHX chips before and immediately after SRP improved CAL and reduced the subgingival microorganisms of the red complex in the treatment of chronic periodontitis.

The interleukin-4 -34TT and -590TT genotype is correlated with increased expression and protein production in aggressive periodontitis.

Aggressive periodontitis (AgP) is a severe periodontal disease characterized by rapid destruction of the tissues supporting the teeth in otherwise healthy individuals. The frequency of the interleukin-4 homozygous -34TT and -590TT genotype was increased in patients in comparison with controls. This study aimed to test the functional effect of this specific genotype in AgP patients by analyzing gene expression of IL-4 and STAT6, and protein concentration of IL-4, in activated CD4+ T cells. Results revealed an increased IL-4 and STAT6 expression and IL-4 production in the cells of the patients who were homozygous for the -34T and -590T alleles in comparison with the patients who were homozygous for the -34C and -590C alleles (p<0.05). These findings demonstrate that the IL-4 -34TT and -590TT genotype has a functional effect on T helper (Th) cells of patients with AgP, inducing increased expression of IL-4 and STAT6, and increased production of IL-4.

A randomized clinical multicentre trial comparing enamel matrix derivative and membrane treatment of buccal class II furcation involvement in mandibular molars. Part III: patient factors and treatment outcome.

OBJECTIVE: Evaluation of effects of patient factors on the outcome of regenerative treatment of buccal mandibular class II furcation defects. MATERIAL AND METHODS: Fifty-one patients were recruited. In the intention-to-treat population 21 patients were allocated into the sequence left treatment with enamel matrix protein derivative (EMD) and right guided tissue regeneration (GTR) and 27 in the sequence left GTR and right EMD. Evaluated patient factors were: smoking, age, gender, hypertension and oral hygiene status. Outcome parameters included change of: (a) horizontal depth of the defect at the deepest point (b) distance from the fornix of the furcation to bone crest of the defect, (c) distance from stent to the bottom of the defect, (d) pocket depth and (e) attachment level at the middle of the furcation. RESULTS: In patients 54 years of age and older, in males, in non-smokers and in patients with "poor" hygiene EMD-treated sites showed a significant higher mean reduction of the parameters d (age), b (gender, hygiene) a (smoking, hygiene) when compared with sites treated with GTR. CONCLUSIONS: These data provided an indication of a possible effect of patient factors on the outcome of regenerative treatment of buccal mandibular class II furcation defects.

A randomized clinical trial comparing enamel matrix derivative and membrane treatment of buccal class II furcation involvement in mandibular molars. Part II: secondary outcomes.

BACKGROUND: This multicenter, randomized trial compared enamel matrix derivative (EMD) with barrier membranes for the treatment of Class II mandibular furcations with regard to secondary outcomes. The influence of furcation morphology on the effectiveness of either treatment was also evaluated. METHODS: Forty-eight patients (age range 28 to 73 years; 22 females, 26 males) with buccal Class II furcation involvements in both contralateral lower first or second molars were included. After initial periodontal treatment, defects were randomized to either EMD or bioabsorbable guided tissue regeneration (GTR) barrier. Study design and the results for the primary parameter were previously described. Results of the following secondary outcome variables are reported here: changes of the hard tissue boundaries describing the anatomical situation of the furcation defect and changes in the following clinical parameters between baseline and 14 months: plaque, level of gingival margin, probing depth, bleeding on probing, attachment level, and bone sounding at five sites/tooth at the buccal side. Descriptive statistics were applied for changes in clinical parameters and measurements of hard tissue boundaries. The differences observed under treatment with EMD or membrane were analyzed by means of the Wilcoxon two-sample test. The difference between the effect of the EMD and membrane treatment was estimated by means of the Hodges-Lehmann estimator. RESULTS: Overall, similar healing results were observed for both treatments. However, there was slightly more recession in the mid-furcation site following membrane treatment (P = 0.04). Additionally, different treatment effects could be detected for the distances from the stent or cemento-enamel junction (CEJ) to the buccal bone crest, mid-distal root (Pstent = 0.01; PCEJ = 0.07) and for the distance from the stent or CEJ to the buccal bone crest, mid-mesial root (Pstent = 0.01; PCEJ = 0.01). There was no measurable bone resorption in EMD sites, whereas a slight resorption occurred with membrane treatment. Furcation morphology at the time of surgery was not associated with clinical outcome, irrespective of the treatment. CONCLUSION: With regard to secondary outcome parameters, enamel matrix derivative treatment led to a similar regenerative result as the membrane procedure.

A randomized clinical trial comparing enamel matrix derivative and membrane treatment of buccal Class II furcation involvement in mandibular molars. Part I: Study design and results for primary outcomes.

BACKGROUND: The objective of this multicenter, randomized trial was to compare enamel matrix derivative (EMD; test) with barrier membranes (control) for the treatment of mandibular buccal Class II furcation defects. METHODS: Forty-five patients with 90 comparable defects on contralateral molars were included. Defects were randomly assigned to EMD or bioabsorbable barrier membrane; the contralateral defect received the alternative treatment. Assessments at baseline and 8 and 14 months included gingival margin levels, probing depths, bleeding on probing, vertical attachment levels, and vertical bone sounding from a stent at five buccal sites/ tooth. Defect dimensions were recorded at surgery and during reentry at 14 months. Change of open horizontal furcation depth was the primary outcome variable. Adverse reactions and patient perceptions were also noted. RESULTS: Both treatment modalities led to significant clinical improvements. The median reduction of open horizontal furcation depth was 2.8 mm with the corresponding interquartile interval (1.5 mm, 3.5 mm) at test sites compared with 1.8 mm (1.0 mm, 2.8 mm) at control sites. The Hodges-Lehmann estimator of the advantage (reduction test versus control) was 0.75 mm (95% confidence interval [CI]: 0.125 mm, 1.375 mm, P = 0.033, Wilcoxon). The frequency of complete furcation closure was 8/45 (test) and 3/45 (control); partial closure, 27/45 in both groups; no change, 9/45 and 11/45, respectively; and deterioration, 1/45 and 4/45, respectively. The frequency of no pain or no swelling at 1 week post-surgery was 62% and 44%, respectively, at the test sites and 12% and 6% at the control sites. CONCLUSION: There was a significantly greater reduction in horizontal furcation depth and a comparatively lower incidence of postoperative pain/swelling following enamel matrix derivative compared to membrane therapy.

'Interleukin-4 gene polymorphism and its relation to periodontal disease in a Brazilian population of African heritage'.

OBJECTIVES: Host modifying factors, such as genetic predisposition, may increase severity of periodontitis. Genetic polymorphisms in interleukin-4 (IL-4) genes seem to influence host response to microbial challenge. Two IL-4 polymorphisms were found in association with asthma and atopy, and later with aggressive periodontitis in Caucasians. There seems to be a trend for racial differences regarding polymorphisms. Therefore, this study aimed to evaluate if these IL-4 polymorphisms were associated with periodontal disease in a Brazilian population of African heritage. METHODS: Sixty patients were divided into two groups: periodontitis group (n = 30) and control group (n = 30) Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 bp repeat polymorphism in intron 2 and in the -590 position of the promoter region was performed through PCR-RFLP and electrophoresis in agarose gel. RESULTS: No significant differences were found in the genotype frequency of the polymorphisms between control and periodontitis group. Chi square test and Mann-Whitney test were used for statistical analysis. CONCLUSIONS: We concluded that the studied IL-4 polymorphisms were not related to periodontal disease susceptibility in this African-American Brazilian population.