Description of lymphocyte and cytokine profiles in individuals with acute myeloid leukemia associated with FLT3-ITD and NPM1 mutation status.

The pathogenesis of acute myeloid leukemia (AML) involves mutations in genes such as FLT3 and NPM1, which are also associated with the prognosis of the disease. The immune system influences disease progression, but the mechanisms underlying the interaction between the immune system and AML are not clear. In this study, the profiles of lymphocytes and cytokines were described in individuals with AML stratified by molecular changes associated with prognosis. The participants included in this study were newly diagnosed AML patients (n = 43) who were about to undergo chemotherapy. Subtypes of lymphocytes in peripheral blood, including B cells, T cells, and natural killer cells, and serum concentrations of cytokines, including Th1, Th2, and Th17, were studied by flow cytometry assays (BD FACSCanto II). The correlations between lymphocyte subsets, cytokines, and genetic/prognostic risk stratification (based on the FLT3 and NPM1 genes) were analyzed. The differences in B lymphocytes (%), T lymphocytes (%), plasmablasts (%), leukocytes (cells/µl), and tumor necrosis factor (pg/ml) were determined between groups with FLT3-ITD+ and FLT3-ITD- mutations. The presence of mutations in NPM1 and FLT3-ITD and age suggested changes in the lymphocyte and cytokine profile in individuals with AML.

Single nucleotide variants in the IL33 and IL1RL1 (ST2) genes are associated with periodontitis and with Aggregatibacter actinomycetemcomitans in the dental plaque biofilm: A putative role in understanding the host immune response in periodontitis.

The Interleukin (IL)-33 is important in several inflammatory diseases and its cellular receptor is the Interleukin 1 receptor-like 1 (IL1RL1), also called suppression of tumorigenicity 2 ligand (ST2L). This study investigated associations between single nucleotide variants (SNVs) in the IL33 gene and in the IL1RL1 (ST2) gene with periodontitis. Additionally, aimed to determine the role of Aggregatibacter actinomycetemcomitans (Aa) relative amount in the subgingival biofilm in these associations. A cross-sectional study was carried out with 506 individuals that answered a structured questionnaire used to collect their health status, socioeconomic-demographic, and behavioral characteristics. Periodontal examination was performed to determine the presence and severity of periodontitis, and subgingival biofilm samples were collected to quantify the relative amount of Aa by real time polymerase chain reaction. Human genomic DNA was extracted from whole blood cells and SNV genotyping was performed. Logistic regression estimated the association measurements, odds ratio (OR), and 95% confidence interval (95%CI), between the IL33 and ST2 genes with periodontitis, and subgroup analyses assessed the relative amount of Aa in these associations. 23% of individuals had periodontitis. Adjusted measurements showed a statistically significant inverse association between two SNVs of the ST2; rs148548829 (C allele) and rs10206753 (G allele). These two alleles together with a third SNV, the rs11693204 (A allele), were inversely associated with moderate periodontitis. One SNV of the IL33 gene also showed a statistically significant inverse association with moderate periodontitis. Nine SNVs of the ST2 gene were inversely associated with the relative amount of Aa. In the high Aa subgroup, there was a direct association between 11 SNVs of the ST2 gene and moderate periodontitis and two SNVs of the ST2 gene and severe periodontitis, and eight SNVs of the ST2 gene and periodontitis. These exploratory findings of genetic variants in IL-33/ST2 axis support the concept that the different tissue responses among individuals with periodontitis may be modulated by the host's genetics, influencing the physiopathology of the disease.

Moderate and severe periodontitis are positively associated with metabolic syndrome.

OBJECTIVE: This study investigated the association between periodontitis severity (exposure) and metabolic syndrome (MetS - outcome), using two criteria for diagnosis of the outcome, since this relationship remains unexplored. MATERIALS AND METHODS: A case-control study was conducted with 870 individuals: 408 with first MetS diagnosis (cases) and 462 without MetS (controls). Participants' general information was obtained using a questionnaire and laboratory data was collected from medical records. Periodontitis severity criteria followed the Center for Disease Control and Prevention: none, mild, moderate, and severe. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. RESULTS: Findings showed a positive association between moderate and severe periodontitis and MetS: ORadjusted = 1.64 (95% CI: 1.01 to 2.68) and ORadjusted = 1.94 (95% CI: 1.19 to 3.16), respectively, after adjustment for age, sex, schooling level, smoking habit, and cardiovascular disease. The adjusted measurements showed that among individuals with moderate or severe periodontitis, the probability of having MetS was around two times greater than among those without periodontitis, and that the chance was greater among participants with severe periodontitis than those with moderate periodontitis. CONCLUSION: An association between the severity of periodontal status and MetS was found, suggesting a possible relationship between the two diseases. CLINICAL RELEVANCE: MetS influences the etiology of cardiovascular diseases, one of the leading causes of mortality worldwide. The findings suggest that the greater the severity of periodontitis, the greater is the association magnitude with MetS. The health professional needs to recognize that the importance of periodontal disease may play in MetS.

Common mental disorder is associated with periodontitis.

OBJECTIVES: This research evaluated the association between exposure to common mental disorder (CMD) and the presence of periodontitis. BACKGROUND: Common mental disorder is characterized by the presence of irritation, fatigue, insomnia, forgetfulness, decreased ability to concentrate, anxiety, and depression. It has been associated with several diseases; however, there are few studies that have associated it with periodontitis. METHODS: This cross-sectional study was carried out with 621 individuals. Data collection involved the application of a general questionnaire and the self-reporting questionnaire for diagnosis of CMD. The diagnosis of periodontitis involved a full mouth periodontal examination using: clinical attachment level, probing depth, and bleeding on probing. Prevalence ratios and 95% confidence intervals between CMD (exposure) and periodontitis (outcome) were obtained. RESULTS: In the final sample, 38.16% (237) of the individuals were classified with CMD. Among these, 28.27% (67) had periodontitis. Association measurements showed that the occurrence of periodontitis among those exposed to CMD is approximately 50% higher than in those without this mental condition, with statistical significance, after adjustment for age, sex, family income, current smoking habit, alcohol beverage consumption, and cardiovascular disease (PRadjusted  = 1.54, 95% CI: [1.13 to 2.10]). CONCLUSIONS: The findings showed a positive association between exposure to CMD and periodontitis, revealing the importance of broadening public actions targeting mental health, which seems to be related to oral health, mainly due to the high frequency of the diseases in the studied sample.

Is there association between stress and periodontitis?

OBJECTIVE: This study estimated the association between stress and periodontitis. MATERIALS AND METHODS: A cross-sectional study was conducted with a sample of 621 individuals. Information about individuals was obtained through a questionnaire. Stress was evaluated using the Perceived Stress Scale. The diagnosis of periodontitis was based on a complete periodontal examination including clinical attachment level, probing depth, and bleeding on probing. Prevalence ratios (PR), crude and adjusted, and their respective 95% confidence intervals (95%CI) were estimated by Poisson regression analysis. RESULTS: In the final sample, 48.47% (301) of the individuals were classified as having stress, of which, 23.92% (72) had the diagnosis of periodontitis. Association measurements between stress and probing depth ≥ 4 mm (PRadjusted = 1.28, 95%CI [1.04 to 1.58]), stress and clinical attachment level ≥ 5 mm (PRadjusted = 1.15, 95%CI [1.01 to 1.31]), and stress and periodontitis (PRadjusted = 1.36, 95%CI [1.01 to 1.83]) showed that the frequency of these outcomes among those exposed to stress was 15-36% higher than those without the condition of stress, after adjustment for age, sex, schooling level, current smoking habit, pulmonary disease, and body mass index. CONCLUSIONS: The findings showed positive association between exposure to stress and the presence of periodontitis, reaffirming the need to prevent and control stress. CLINICAL RELEVANCE: Although there are limitations in this study, the results showed that an association exists between stress and periodontitis, signaling the necessity of a multidisciplinary attention when considering the psychological status in the management of oral and general health conditions of the individual.

Production of interferon-gamma, interleukin-6, and interleukin-1ß by human peripheral blood mononuclear cells stimulated with novel lys-gingipain synthetic peptides.

BACKGROUND: Periodontitis is a progressive inflammatory process, and its pathogenesis is related to the presence of a dysbiotic subgingival biofilm that elicits the immune response. Porphyromonas gingivalis is a keystone pathogen, and its Lys-gingipain (Kgp) virulence factor is involved in the pathogen-host interaction through the production of cytokines by host cells, but the specific mechanisms of this interaction have not been elucidated. The present study evaluated the in vitro production of interferon-gamma (IFN-γ), interleukin (IL)-6, and IL-1ß cytokines in response to antigenic stimulation of peripheral blood mononuclear cells (PBMCs) with novel Kgp synthetic peptides. METHODS: Our previous in silico study predicted 16 immunogenic peptides from Kgp protein. Nine peptides derived from different regions of the protein were chemically synthesized. The synthetic peptides Kgp12, 17, and 18 were selected based on the immunoglobulin G immunoreactivity in the serum of patients with periodontitis (P) and individuals without periodontitis (WP), and they were used in in vitro stimulation of PBMC derived from groups P and WP. Enzyme-linked immunosorbent assay and microsphere-based flow cytometric assay were used to verify the levels of the cytokines produced in PBMC cultures after 48 hours. RESULTS: Kgp12, 17, and 18 peptides induced lower production of IFN-γ. Kgp12 induced higher levels of IFN-γ in WP than in P individuals. Kgp12 induced higher production of IL-6 and IL-1ß compared with the other stimuli. CONCLUSION: The novel Kgp synthetic peptides tested herein are immunogenic peptides (epitopes) since they induced the production of cytokines by PBMC and therefore may be useful tools in evaluating the pathogen-host interaction.

Association between osteoporosis treatment and severe periodontitis in postmenopausal women.

OBJECTIVE: To estimate the association between osteoporosis treatment and severe periodontitis in postmenopausal women. METHODS: This cross-sectional study comprised of 492 postmenopausal women, 113 women in osteoporosis treatment, and 379 not treated. Osteoporosis treatment consisted of systemic estrogen alone, or estrogen plus progestin, and calcium and vitamin D supplements, for at least 6 months. Severe periodontitis was defined as at least two interproximal tooth sites with clinical attachment loss of at least 6 mm, and at least one interproximal site with probing depth of at least 5 mm; and dental caries experience was measured using the decayed, missing, and filled teeth (DMFT) index. Analysis included descriptive statistics and Poisson multivariate analysis with robust variance. RESULTS: Women receiving osteoporosis treatment had less periodontal probing depth, less clinical attachment loss, and less gingival bleeding than women not receiving treatment for osteoporosis (P ≤ 0.05). In the osteoporosis treatment group, the estimated mean DMFT index score was approximately 20, the most frequent component being the number of missing teeth, and in the nontreated group, the DMFT index was approximately 19. The prevalence of severe periodontitis was 44% lower in the osteoporosis treatment group than in the nontreatment group. The prevalence ratioadjusted was 0.56, 95% confidence interval was 0.31 to 0.99 (P = 0.05), after adjustments for smoking, age, family income, and visit to the dentist. CONCLUSIONS: The results suggest that women treated with estrogen for postmenopausal osteoporosis have a lower prevalence of severe periodontitis than women not receiving treatment.

Immune response of macrophages induced by Porphyromonas gingivalis requires HmuY protein.

The main etiologic agent and a key pathogen responsible for initiation and progression of chronic periodontitis is Porphyromonas gingivalis. We examined the role of P. gingivalis, with particular interest to HmuY protein, in expression of genes involved in Toll-like receptor (TLR)-induced signaling pathways using cell-based infection model. U937 and THP-1 cells differentiated toward macrophages by PMA treatment responded to P. gingivalis-caused infection in slightly different gene expression pattern, mainly by higher expression of genes encoding NF-κB, TLR7, TLR2, TLR8, pro-inflammatory cytokines (IL-1ß, IL-6, TNFα), anti-inflammatory cytokine (IL-10), and chemokines (CCL3L1, CCL4, CXCL10, CXCL11, PTX3). P. gingivalis lacking functional hmuY gene stimulates immune response of macrophages, albeit in a different manner as compared with the wild-type strain, mainly by lower expression of genes encoding NF-κB, IL-1ß, IL-10, CD80, PTX3, and CCL31L. The purified HmuY protein alone induced expression of genes encoding IL-6, IL-10, TNFα, CCL3L1, and CCL4. We conclude that macrophages respond to P. gingivalis infection mostly by TLR7-induced pathway(s). Moreover, P. gingivalis HmuY is one of important virulence factors, which allows P. gingivalis for in vivo growth in the heme-limited host environment, resulting in efficient immune response of macrophages.

Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human CD3+ T cells.

BACKGROUND: Apoptosis is a highly controlled process of cell death that can be induced by periodontopathogens. The present study aimed to investigate the expression of Fas and Bcl-2 proteins by CD3+ T cells in vitro under stimulation by total Porphyromonas gingivalis antigens and purified recombinant P. gingivalis HmuY protein. RESULTS: CD3+ T cells derived from CP patients and stimulated with HmuY expressed higher levels of Bcl-2 compared to identical cells stimulated with P. gingivalis crude extract or cells derived from NP control subjects (p = 0.043). CONCLUSION: The authors hypothesize that P. gingivalis HmuY plays a role in the pathogenesis of chronic periodontitis, possibly by reducing or delaying apoptosis in T cells through a pathway involving the Bcl-2 protein.

Women with low bone mineral density and dental panoramic radiography.

OBJECTIVE: The aim of this study was to investigate whether some mandibular measurements on panoramic radiographs are associated with low bone mineral density in postmenopausal women. METHODS: A sample of 122 panoramic dental radiographs and bone density tests from women 50 years or older were examined. Bone mineral density was measured in the lumbar spine and proximal femur regions through dual-energy x-ray absorptiometry. The mandibular cortical bone thickness below the mental foramen, mandibular alveolar bone resorption, and panoramic mandibular index were measured. RESULTS: The mandibular cortical thickness and mandibular alveolar bone resorption showed the highest specificity (lumbar spine: 89.8% vs 73.5%, proximal femur: 83.6% vs 71.2%, respectively). The panoramic mandibular index demonstrated the highest sensitivity (lumbar spine: 43.8%; proximal femur: 40.8%). The association between the mandibular cortical thickness and bone mineral density was statistically significant even after adjustment for hormonal treatment, smoking, age at menopause, and body mass index (P = 0.04). CONCLUSIONS: It is suggested that panoramic radiography may be useful for confirming individuals who present with low bone mineral density.

Humoral immune response to antigens of Porphyromonas gingivalis ATCC 33277 in chronic periodontitis

Introduction: Periodontitis is a chronic disease that results from an interaction of a mixed bacterial challenge and the host response. Objective: The purposes of this study were to evaluate the IgG serum levels to Porphyromonas gingivalis antigens by ELISA in individuals with different periodontal conditions correlated with clinical parameters, and to analyze the immunoreactivity profiles by Western blotting. Methods: Serum IgG levels against the cell sonicate antigen from P. gingivalis ATCC 33277 of 28 patients with chronic periodontitis (CP), 10 patients with gingivitis (G) and 21 periodontally healthy individuals (H) were measured by ELISA and Western immunoblotting. Results: In the CP group, sera reactivity by ELISA was significantly higher than in the G and H groups (Kruskal-Wallis p<0.001; Dunnet t3 p= 0.001 and Dunnet t3 p= 0.0001). There was no statistically significant difference between G and HP reactivity (Dunnett t3 p=0.617). Among individuals with chronic periodontitis, the IgG-anti-P. gingivalis serum levels were positively correlated with percentage of clinical attachment level =5mm (r s = + 0.375, p<0.05) and a negative correlation was found between IgG-anti-P. gingivalis levels and percentage of probing pocket depth 0-3mm (r s = - 0. 411, p< 0.05). The analysis of sera immunoreactivity profiles to sonicate antigen by Western blotting showed differences between the sera of CP, G and H group individuals. The serum from CP frequently reacted with high molecular weight (103 kDa, 86 kDa, 72 kDa, 60 kDa, 58 kDa, 52 kDa) protein fractions. Conclusions: Serum levels of IgG anti-P. gingivalis distinguished individuals with chronic periodontitis, gingivitis and healthy periodontium. There was a correlation between clinical parameters and serum IgG levels against P. gingivalis. There was a difference in the recognition profile of protein fractions among the studied groups and some bands were more specific.

Periodontal status as predictor of prematurity and low birth weight.

OBJECTIVE: The objective was to verify the relation between periodontal status and prematurity/low birth weight. METHODS: a case control study of 211 women, 44 being mothers of children born with weight below 2.500g or gestational age of less than 37 weeks (case group) and 177 mothers of children born with weight of over 2.500g or more and gestational age of 37 weeks or more (control group). The women were invited to reply to a questionnaire during the interview. A single dentist performed a complete periodontal exam in the oral cavity of each participant, including: probing depth, recession, plaque index, bleeding on probing, and clinical attachment loss measurements. Descriptive analysis of the study variables was performed and the statistical significance was calculated at 5%, using the chi-squared test. RESULTS: There was no statistically significant difference in the clinical parameters between the groups. CONCLUSIONS: The findings showed no association between periodontal status and prematurity/low birth weight.