Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients.

OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic immuno-inflammatory conditions with osteolysis being a hallmark feature. The influence of PD on RA's systemic inflammatory status and disease activity remains unclear. The objective of this study was to assess the systemic inflammation and disease activity of RA under the influence of PD. METHODS: In this case-control study, 38 RA patients (19 with PD and 19 without PD) were compared to 38 non-RA patients and 12 healthy controls. Periodontal parameters (bleeding on probing (BOP), probing pocket depth (PPD), PPD Total, PPD Disease and marginal bone loss (MBL) were determined. Serological analyses included quantification of 92 inflammatory biomarkers using a multiplex proximity extension assay, anti-citrullinated protein antibodies (ACPA), rheumatoid factor (IgM-RF) and erythrocyte sedimentation rate (ESR). RA disease activity was determined using Disease Activity Score for 28 joints (DAS28). All RA patients were on medication. RESULTS: IgM-RF was higher in RA patients with PD. PD conditions were more severe in the non-RA group. Inflammatory biomarkers (IL-10RB, IL-18, CSF-1, NT-3, TRAIL, PD-L1, LIF-R, SLAMF1, FGF-19, TRANCE, CST5, STAMPB, SIRT2, TWEAK, CX3CL1, CXCL5, MCP-1) were significantly higher in RA patients with PD than RA without PD. DAS28 associated with twice as many inflammatory biomarkers in RA patients with PD whereas IgM-RF and ACPA associated more frequently with biomarkers in the RA without PD group. IgM-RF correlated inversely with BOP. CONCLUSION: Periodontal disease augments systemic inflammation in RA. A profound influence exists independent of autoimmune status.

Pre-diabetes and diabetes: Medical risk factors and periodontal conditions.

OBJECTIVE: The aim of this study was to evaluate the difference between subjects with pre-diabetes, well or poorly controlled diabetes mellitus type 2 (T2D) and non-diabetes concerning such medical risk factors as hemoglobin A1c, body mass index (BMI) and waist circumference (WC) with periodontal conditions. MATERIALS AND METHODS: BMI, WC, PI, BOP, PD and marginal bone level (MBL) were recorded. Hemoglobin A1c (HbA1c) level and random blood glucose level (RBGL) were analyzed. RESULTS: Forty-five subjects were pre-diabetics, 64 subjects had poorly controlled T2D, 28 subjects had well controlled T2D and 76 subjects were non-diabetics. Non-diabetics, pre-diabetics as well as subjects with T2D were overweight. Females in all groups had increased mean levels of WC. Number of PD ≥ 6 mm were increased in subjects with poorly controlled T2D compared to non-diabetics and pre-diabetics (p < 0.05). CONCLUSIONS: Pre-diabetic subjects showed the same periodontal conditions as non-diabetic subjects. Forty-five of the subjects reporting to have no diabetes were pre-diabetics. Non-diabetic, pre-diabetic and diabetic subjects were overweight. Subjects with poorly controlled T2D had severe periodontal conditions.

Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis.

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. Methods: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein−protein interaction (PPI) networks. Results: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. Conclusion: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status.

Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender.

BACKGROUND: The association between periodontal conditions, oral yeast colonisation and salivary proteins in subjects with type 2 diabetes (T2D) is not yet documented. The present study aimed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender. METHODS: Fifty-eight type 2 diabetic subjects (23 males and 35 females) with random blood glucose level >or= 11.1 mmol/L were investigated. Periodontal conditions (plaque index [PI], bleeding on probing [BOP], probing pocket depth [PD] (4 to 6 mm and >or= 6 mm), oral yeasts, salivary immunoglobulin (Ig) A, IgG and total protein concentrations, and number of present teeth were determined. RESULTS: Periodontal conditions (PI [p < 0.00001], BOP [p < 0.01] and PD of 4 to 6 mm [p < 0.001], salivary IgG (microg)/mg protein (p < 0.001) and salivary total protein concentrations (p < 0.05) were higher in type 2 diabetic females with Candida albicans (C. albicans) colonisation compared to males in the same group. Type 2 diabetic females with C. albicans colonisation had more teeth compared to males in the same group (p < 0.0001). CONCLUSION: Clinical and salivary parameters of periodontal inflammation (BOP and IgG (mug)/mg protein) were higher in type 2 diabetic females with oral C. albicans colonisation compared to males in the same group. Further studies are warranted to evaluate the association of gender with these variables in subjects with T2D.

Periodontal conditions and oral symptoms in gutka-chewers with and without type 2 diabetes.

OBJECTIVE: The aim of the study was to investigate the periodontal conditions and oral symptoms among gutka-chewers in subjects with and without type 2 diabetes (T2D). MATERIAL AND METHODS: Subjects aged between 45 and 64 years were included. "Gutka-chewers" were defined as subjects who had been chewing at least one sachet of gutka daily for at least 12 months. Subjects who reported never to have used tobacco in any form were categorized as "non-chewers". Periodontal conditions (plaque index [PI], bleeding on probing [BOP], and probing depth [PD] [4 mm<6 mm and > or =6 mm]), number of missing teeth, oral symptoms, reasons for gutka use, and random blood glucose levels were recorded. Exclusion criteria were smoking and use of antibiotics, non-steroidal anti-inflammatory drugs, and steroids. RESULTS: Mean durations of gutka use in subjects with and without T2D were 10.5 (range 8.0-15.5 years) and 8.4 (range 6.0-20.2 years) years correspondingly. In subjects with T2D, gutka-chewers (n=29) and non-chewers (n=44) showed no difference in periodontal conditions, missing teeth, and gingival bleeding. In subjects without T2D, gutka-chewers (n=36) had increased PI (p<0.01), BOP (p<0.001), PD (4 mm<6 mm) (p<0.01), number of missing teeth, and gingival bleeding (p<0.01) compared to non-chewers (n=42). Non-chewers in subjects with T2D had poorer periodontal conditions and increased oral symptoms compared to gutka-chewers and non-chewers in subjects without T2D. CONCLUSION: In subjects without T2D, gutka-chewers have severe periodontal conditions and oral symptoms compared to non-chewers. In subjects with T2D, the severity of these variables is related to glycemic levels rather than gutka consumption.

Periodontal disease influences osteoclastogenic bone markers in subjects with and without rheumatoid arthritis.

BACKGROUND: Periodontal disease (PD) and rheumatoid arthritis (RA) are bone pathologies mediated through immuno-inflammatory mechanisms. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor-kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups. MATERIALS & METHODS: RA (with PD = 19 and without PD = 19), PD (n = 38) and 14 healthy subjects underwent bleeding on probing (BOP) and probing pocket depth (PPD) measurement. PD was defined as PPD measuring ≥5mm registered in ≥3 sites. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. Serum samples were collected from all subjects. OPN, TNFR1, TNFR2 and RANKL were measured by enzyme-linked immunosorbent assays (ELISAs). OPG was measured as part of a multiplex proximity extension assay (PEA). RESULTS: OPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37). Serum RANKL levels were associated with MBL (p = 0.008) and PPD ≥ 5mm (p = 0.01). CONCLUSION: Peripheral osteoclastogenesis is a feature of periodontal disease with systemic levels of osteoclastogenic markers comparable to the effects observed in rheumatoid arthritis.

Comparison of periodontal and socioeconomic status between subjects with type 2 diabetes mellitus and non-diabetic controls.

BACKGROUND: The association among periodontal conditions, socioeconomic status (SES), and diabetes has been reported. However, there is a lack of published data comparing periodontal conditions among individuals with poorly controlled type 2 diabetes mellitus (T2D). The aim of the present study was to compare the periodontal conditions and SES between subjects with T2D and non-diabetic controls. METHODS: A total of 75 (31 males and 44 females) individuals with T2D (62 poorly controlled and 13 well-controlled) and 99 non-diabetic patients (healthy controls; 51 males and 48 females) participated in the study. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were investigated. Random blood glucose level was recorded. Premolar and molar marginal bone loss (MBL) was measured digitally on scanned orthopantomograms. RESULTS: Individuals with poorly controlled T2D had increased MBL in molars and maxillary premolars (P<0.05) compared to individuals with well-controlled T2D. PI, BOP, and PD of 4 to <6 mm were increased in individuals with poorly controlled T2D compared to those with well-controlled T2D (P<0.001). There was no difference between the diabetic groups when PD was >or=6 mm. Individuals with poorly controlled T2D had a lower SES compared to patients with well-controlled T2D (P<0.05). Illiteracy and the number of missing teeth were not different between the groups. CONCLUSIONS: Radiologic and clinical indicators of periodontal destruction were increased in individuals with poorly controlled T2D. Low SES aggravated the periodontal condition in individuals with T2D.

Measurement accuracy of marginal bone level in digital radiographs with and without color coding.

OBJECTIVE: New radiographic techniques have made it possible to color-code intra-oral digital radiographs. The purpose of the present study was to compare the accuracy and precision of marginal bone level measurements in digital radiographs with and without color coding. MATERIAL AND METHODS: Periapical digital radiographs of 21 patients were processed with and without a color-coding algorithm. The patients had periodontal surgery immediately after exposure of radiographs, and vertical distances from the cemento-enamel junction (CEJ) to the most apical part of the marginal bone were measured clinically. The measured values were considered as a reference standard and subtracted from the corresponding radiographic vertical distance. Seven observers contributed to the radiographic measurements under the same viewing conditions. RESULTS: No statistically significant differences were found between absolute differences of vertical distances obtained from radiographs and their corresponding reference standards in the two types of radiograph. Intra- and inter-observer variability was not significant. CONCLUSION: Color-coded digital radiographs did not provide a more favorable accuracy when assessing marginal alveolar bone levels than black-and-white radiographs and thus did not improve measurement of such levels.

Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters.

BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14). Bleeding on probing (BOP) and probing pocket depth (PPD) were measured. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. PD was defined as present if the PPD was ≥5mm in ≥ 3 different sites. Serum samples were collected from all subjects. A multiplex proximity extension assay (PEA) was used to analyze the samples for simultaneous measurement of 92 cytokines. Cytokines with ≥ 60% quantitative results were included. RESULTS: A significant positive correlation was seen for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and TWEAK associated inversely with BOP, PPD≥ 5mm and MBL but positively with number of teeth. Several CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6) were found to be associated with BOP, shallow and deep pockets, MBL and number of teeth, either directly or inversely. Most chemokines (CCL8, CX3CL1, CXCL10, CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23) were positively associated with number of teeth and some inversely related to MBL (CCL8, CXCL10). Proteins with enzymatic activity (ST1A1, HGF and CASP-8) were directly related to the severity of periodontal conditions and inversely related to number of teeth. Aside from FGF-19, other growth factors were also directly associated with MBL (HGF), number of teeth (VEGF-A, LAP TGF-beta-1) and, inversely to, shallow pockets (LAP TGF-beta-1, TGFA and Beta-NGF). Out of 33 cytokines, 32 associated inversely with shallow pockets, whereas only CD40 associated positively. Associations between cytokines and periodontal parameters in the RA group were comparatively less. Statistical analyses were adjusted for multivariate effects using the Benjamini-Hochberg false discovery rate method. CONCLUSION: Systemic inflammatory burden, via known and novel markers, is associated with periodontal conditions in PD and RA subjects. Shallow pockets are not associated with a higher inflammatory state.

Specific IgA subclass responses in serum and saliva: a 12-month follow-up study after parenteral booster immunization with tetanus toxoid.

Specific IgA subclass antibodies against tetanus toxoid in serum, parotid saliva, and whole saliva were quantified after booster immunization. Samples from 14 healthy individuals were collected before and 1, 6, and 12 months after subcutaneous injection with Duplex (0.23 ml tetanus toxoid 30 Lf/mL and diphtheria 7.3 Lf/mL). Samples of whole saliva were also collected after 2 weeks. Specific IgA1 and IgA2 subclass antibodies to tetanus toxoid were quantified by enzyme-linked immunosorbent assay (ELISA). In this quantitative method, chimeric IgA1 and IgA2 antibodies directed against NP (4-hydroxy-3-nitrophenacetyl) were used as standards. Total levels of IgA1 and IgA2 were measured using a nephalometer or ELISA. Immunization with tetanus toxoid resulted in raised mean values of specific IgA1 and IgA2 antibodies against tetanus toxoid in serum after 1 month. Compared with the baseline, the mean value of specific IgA1 antibodies showed a 2.6-fold increase (mean value 10.47 microgram/mL) in serum, and that of specific IgA2 antibodies a 2.7-fold increase (mean value 0.93 microgram/mL). Specific IgA subclass antibody levels in parotid and whole saliva were unchanged after 1 month. The ratio of specific IgA subclass antibodies to total IgA subclass antibodies was 3 to 10 times higher in parotid saliva compared with whole saliva. In conclusion, subcutaneous booster immunization with tetanus toxoid induced immune responses of both antigen-specific IgA1 and IgA2 subclass antibodies in serum with the same increase, whereas the levels of specific IgA subclass antibodies in secretory fluids were unchanged. The ratio of specific IgA subclass antibodies to immunoglobulins was higher in parotid saliva compared with whole saliva.