The authors have taken the liberty of presenting this manuscript in two parts. The first is a brief primer on microbial ecology, because, although the importance of microbial ecology in periodontal diseases is widely recognized, most of us do not know precisely what is meant by the term. The second section is a rather extensive overview of current studies of oral microbial ecology based almost entirely on recent in vivo studies.

https://laurieximenez.files.wordpress.com/2011/02/ref-2_socransky-2005_p2000.pdf

Periodontal microbial ecology.

Background Authors were assigned the task to develop case definitions for periodontitis in the context of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The aim of this manuscript is to review evidence and rationale for a revision of the current classification, to provide a framework for case definition that fully implicates state-of-the-art knowledge and can be adapted as new evidence emerges, and to suggest a case definition system that can be implemented in clinical practice, research and epidemiologic surveillance. Methods Evidence gathered in four commissioned reviews was analyzed and interpreted with special emphasis to changes with regards to the understanding available prior to the 1999 classification. Authors analyzed case definition systems employed for a variety of chronic diseases and identified key criteria for a classification/case definition of periodontitis. Results The manuscript discusses the merits of a periodontitis case definition system based on Staging and Grading and proposes a case definition framework. Stage I to IV of periodontitis is defined based on severity (primarily periodontal breakdown with reference to root length and periodontitis-associated tooth loss), complexity of management (pocket depth, infrabony defects, furcation involvement, tooth hypermobility, masticatory dysfunction) and additionally described as extent (localized or generalized). Grade of periodontitis is estimated with direct or indirect evidence of progression rate in three categories: slow, moderate and rapid progression (Grade A-C). Risk factor analysis is used as grade modifier. Conclusions The paper describes a simple matrix based on stage and grade to appropriately define periodontitis in an individual patient. The proposed case definition extends beyond description based on severity to include characterization of biological features of the disease and represents a first step towards adoption of precision medicine concepts to the management of periodontitis. It also provides the necessary framework for introduction of biomarkers in diagnosis and prognosis.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcpe.12945

Staging and grading of periodontitis: Framework and proposal of a new classification and case definition.

Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions

The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm.

/pdf/cytokine-gene-polymorphism-in-human-disease-on-line-mb7yqxfth5.pdf

Cytokine gene polymorphism in human disease: on-line databases.

Interleukin (IL)-1 and tumor necrosis factor (TNF) represent proinflammatory cytokines that stimulate a number of events which occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. The use of antagonists to IL-1 and TNF in experimental periodontitis have demonstrated a cause-and-effect relationship between the activity of these cytokines and the spread of an inflammatory front to deeper areas in the connective tissue, loss of connective tissue attachment, osteoclast formation, and loss of alveolar bone. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is, in part, mediated by TNF. Thus, much of the damage that occurs during periodontal tissue ...

The Contribution of Interleukin-1 and Tumor Necrosis Factor to Periodontal Tissue Destruction

Although specific bacteria, dental plaque, and age are associated with periodontal disease, there are currently no reliable predictors of periodontitis severity. Studies in twins have suggested a genetic contribution to the pathogenesis of periodontitis, but previous attempts to identify genetic markers have been unsuccessful. The pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are key regulators of the host responses to microbial infection. IL-1 is also a major modulator of extracellular matrix catabolism and bone resorption. We report a specific genotype of the polymorphic IL-1 gene cluster that was associated with severity of periodontitis in non-smokers, and distinguished individuals with severe periodontitis from those with mild disease (odds ratio 18.9 for ages 40-60 years). Functionally, the specific periodontitis-associated IL-1 genotype comprises a variant in the IL-1B gene that is associated with high levels of IL-1 production. In smokers severe disease was not correlated with genotype. In this study, 86.0% of the severe periodontitis patients were accounted for by either smoking or the IL-1 genotype. This study demonstrates that specific genetic markers, that have been associated with increased IL-1 production, are a strong indicator of susceptibility to severe periodontitis in adults.

Frederick W. Pirk

Papers

The interleukin-1 genotype as a severity factor in adult periodontal disease