Periodontitis As an Immunological Disorder: Biomarkers, Treatment, and Maintenance

The association between bacteria and gingivitis has long been established. However, it has recently been determined that the progression from gingivitis to periodontitis only occurs in certain susceptible hosts. Several factors have been identified as posing an increased risk of this progression. Jan Kowalski, Dr. habil., Medical University of Warsaw, Poland, and coauthors wrote, “Almost all of them are connected — directly or indirectly — with immune response.” While increased bacterial load may still play a role, the non-specific component of the immune response is more integral to the destruction of periodontal tissues.

There is a link between gene polymorphisms, host response level, and periodontal inflammation, which validates the search for potential markers of periodontal onset or progression. Finding such markers would allow providers to efficiently screen patients to reach those more likely to require more frequent or thorough prophylaxis, as well as reduce the clinical load of tending to the rest of the population.

Sources for such potential markers include crevicular fluid of gingival sulcus, serum transudate from the pocket, or saliva. Regarding the gingival crevicular fluid and saliva, biomarkers were present prior to the clinically visible effects of periodontal tissue destruction. There have been over 90 possible biomarkers evaluated from the gingival crevicular fluid source. Some possibilities for biomarkers include endogenous MMPs (particularly MMP-8), inflammatory mediators (TNF-alpha, IL-6, and IL-1), prostaglandin E2, RANKL/OPG ratio, and markers related to oxidative stress. There is also evidence that suggests antibody levels may be useful.

Traditionally, periodontitis has been treated with improvement of oral hygiene and professional tooth cleaning. More recently, there has been a focus on immunomodulation, in order to suppress the over-reaction of the immune system and neutralize their effects. Doxycycline, in the subantimicrobial dose (SDD), can be used for severe conditions of periodontitis. While there is rationale for the use of non-steroid anti-inflammatory drugs (NSAIDS), there is a long history of multiple adverse events and NSAIDS have since not be recommended for treating patients with periodontitis. In the last few years, there has been a focus on polyunsaturated omega-3 fat acids (PUFAs) and exosomes, though this research is currently in preclinical stages.

Dr Kowalski et al also addressed the matter of reactive oxygen species (ROS) and chronic oxidative stress, which can eventually lead to the degradation of surrounding tissues. This effect can be combated through therapy and dietary habit. There is evidence demonstrating resveratrol, a naturally occurring polyphenol, can promote fibroblast activity and inhibit bone resorption, as well as neutralize the pathological pathways of a key periopathogens (Porphyromonas gingivalis). The antioxidant curcumin may potentially decrease osteoclastic activity marked by RANKL/OPG ratio. Other research has suggested, “low-sugar food, rich in omega-3 acids and antioxidants would prove beneficial…for periodontal tissues,” wrote Dr Kowalski et al.

The recent understanding of periodontitis as an immunological disorder has helped to clarify its association with systemic diseases such as diabetes, cardiovascular disorders, preterm low birth weight, Alzheimer disease, as well as others. While the nature of the connection is not known in all of the aforementioned cases, there is the common factor of inflammation and circulating immunomediators. This shift to regarding periodontitis as a hyper-reactive response of the immune system has brought the potential of further possibilities for prophylaxis, treatment and maintenance of patients as the fields of both periodontology and immunology advance.

Source:

Kowalski J, Nowak M, Górski B, et al. What has immunology brought to periodontal disease in recent years? Arch Immunol Ther Exp. 2002;70(26).