Local and systemic biomarkers in gingival crevicular fluid increase odds of periodontitis

AimTo determine the independent and combined associations of interleukin-1beta (IL-1beta) and C-reactive protein (CRP) in gingival crevicular fluid (GCF) on periodontitis case status in the Australian population.Materials and methodsGCF was collected from 939 subjects selected from the 2004-2006 Australian National Survey of Adult Oral Health: 430 cases had examiner-diagnosed periodontitis, and 509 controls did not. IL-1beta and CRP in GCF were detected by enzyme-linked immunosorbent assays. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated in bivariate and stratified analysis and fully adjusted ORs were estimated using multivariate logistic regression.ResultsGreater odds of having periodontitis was associated with higher amounts of IL-1beta (OR=2.4, 95% CI=1.7-3.4 for highest tertile of IL-1beta relative to lowest tertile) and CRP (OR=1.9, 95% CI=1.5-2.5 for detectable CRP relative to undetectable CRP). In stratified analysis, there was no significant interaction between biomarkers (p=0.68). In the multivariate analyses that controlled for conventional periodontal risk factors, these relationships remained (IL-1beta OR=1.8, 95% CI=1.1-2.6; CRP OR=1.7, 95% CI=1.3-2.3).ConclusionsElevated odds of clinical periodontitis was associated independently with each biomarker. This suggests that people with elevated biomarkers indicative of either local (IL-1beta) or systemic (CRP) inflammation are more likely to suffer from periodontal disease.Tracy R. Fitzsimmons, Anne E. Sanders, P. Mark Bartold and Gary D. Slad

The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation

Aim To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. Materials & Methods Periodontitis, healthy periodontal and RA-affected synovial tissue samples were collected in addition to buccal swabs. These samples were stained for the presence of citrullinated proteins using polyclonal (Ab5612) and monoclonal (F95) antibodies. Furthermore, Western blotting with F95 was performed on lysates prepared from periodontal and synovial tissues. Results In periodontitis stroma, increased citrullinated protein presence (80%) was observed compared with control stroma (33%), the latter was associated with inflammation of non-periodontitis origin. Periodontal epithelium always stained positive for Ab5612. Noteworthy, only periodontitis-affected epithelium stained positive for F95. All buccal mucosal swabs and 3 of 4 synovial tissue samples stained positive for both Ab5612 and F95. Western blotting with F95 showed presence of similar citrullinated proteins in both periodontitis and RA-affected synovial tissue. Conclusion Within the periodontal stroma, citrullination is an inflammation-depended process. In periodontal epithelium, citrullination is a physiological process. Additional citrullinated proteins are formed in periodontitis, apparently similar to those formed in RA-affected synovial tissue. Periodontitis induced citrullination may play a role in the aetiology of rheumatoid arthritis

Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis

Background: Rheumatoid arthritis (RA) and periodontitis are both chronic inflammatory diseases, which demonstrate similarities in terms of mechanism, histopathology, and demography. An association between these conditions has been demonstrated previously but has been called into question more recently. Methods: The published databases, such as MEDLINE, EMBASE, and PsycINFO, were searched using search terms related to RA and periodontitis. Articles were selected if they included data on the number of people with RA diagnosed with periodontitis (or periodontal disease parameters) compared to a control comparison group. Review articles, case reports, animal model studies, non-English language, and articles with unavailable abstracts were excluded. Data were extracted, critically appraised using the Downs and Black tool, and a random-effect Mantel–Haenszel meta-analysis was performed. Results: Twenty-one papers met the eligibility criteria and provided data for the meta-analysis; 17 studies (including a total of 153,492 participants) comparing RA to healthy controls and 4 (including a total of 1378 participants) comparing RA to osteoarthritis (OA). There was a significantly increased risk of periodontitis in people with RA compared to healthy controls (relative risk: 1.13; 95% CI: 1.04, 1.23; p = 0.006; N = 153,277) with a significantly raised mean probing depth, risk of bleeding on probing (BOP), and absolute value of clinical attachment loss in those with RA. When comparing RA and OA, there was no significant difference in the prevalence of periodontitis; however, the risk of BOP was greater in OA than RA. Conclusion: A significant association between RA and periodontitis is supported by the results of our systematic review and meta-analysis of studies comparing RA to healthy controls. In our meta-analysis, however, this is not replicated when comparing RA to OA controls

Vitamin D in autoimmunity: Molecular mechanisms and therapeutic potential

Over the last three decades, it has become clear that the role of vitamin D goes beyond the regulation of calcium homeostasis and bone health. An important extraskeletal effect of vitamin D is the modulation of the immune system. In the context of autoimmune diseases, this is illustrated by correlations of vitamin D status and genetic polymorphisms in the vitamin D receptor with the incidence and severity of the disease. These correlations warrant investigation into the potential use of vitamin D in the treatment of patients with autoimmune diseases. In recent years, several clinical trials have been performed to investigate the therapeutic value of vitamin D in multiple sclerosis, rheumatoid arthritis, Crohn's disease, type I diabetes, and systemic lupus erythematosus. Additionally, a second angle of investigation has focused on unraveling the molecular pathways used by vitamin D in order to find new potential therapeutic targets. This review will not only provide an overview of the clinical trials that have been performed but also discuss the current knowledge about the molecular mechanisms underlying the immunomodulatory effects of vitamin D and how these advances can be used in the treatment of autoimmune diseases