Clinical Research Center for Periodontal Diseases
The Clinical Research Center for Periodontal Diseases studies periodontal (gum) diseases with emphasis on a group of diseases in teenagers and young adults called early-onset periodontitis.
This form of periodontal disease is significant because it occurs mainly in the African-American population in the U.S. and runs in families and thus could have a genetic cause. Also, patients with the disease have some unusual host-response, or immune-function, characteristics which also could be genetic or influenced by race. These diseases include some of the most severe forms of periodontal disease and can lead to loss of many permanent teeth during the teens and early 20s.
The CRCPD represents an interdisciplinary effort that involves investigators in the VCU schools of Dentistry and Medicine, as well as investigators at the National Institutes of Health, who collaborate on the human genetics aspects of the work. Our work on these diseases began in the late 1970s and continues to date, resulting in accumulation of data and laboratory samples on the largest number of EOP patients and their families in the world.
The goals of ongoing projects in the CRCPD include the following:
- Genetic epidemiology and molecular gene-mapping studies of early onset periodontitis
Investigation of the underlying genetic, or inherited, factors that may cause EOP
Clinical investigators at VCU recruit families of individuals with EOP, perform clinical characterizations and send DNA samples to the genetics laboratory at the National Institute of Dental and Craniofacial Research. The genetics group is searching for a gene or genes that predispose to risk for EOP. Additionally, they are utilizing data from the other CRCPD research groups, such as information about unusual immune responses in these patients, to search for genes that influence these immune responses.
Project director: Scott R. Diehl, Ph.D., NIDCR/NIH
- Monocyte derived lipid mediators and cytokines in regulating IgG2 production
in early-onset periodontitis
Examination of the mechanisms explaining the unusual antibody responses observed in patients with localized juvenile periodontitis, a form of EOP
Patients with LJP produce very high concentrations of a particular antibody protein called IgG2. This type of antibody is usually produced by the body during infections with many kinds of bacteria, including the ones thought to be most involved in LJP. Furthermore, IgG2 is mainly produced as a response against foreign carbohydrates, which are found on most bacteria. Since very high antibody responses are characteristic of LJP patients, we are seeking to determine why LJP patients make so much of this protein. We are examining the various factors that influence one’s ability to make IgG2, including mediators of inflammation such as prostaglandins and other lipids and cytokines (which are proteins produced by cells to signal other cells). In addition, we are closely studying a type of cell called the dendritic cell as a possible cause of the excess IgG2 production by LJP patients.
Project director: John G. Tew, Ph.D., Department of Microbiology and Immunology, VCU School of Medicine.
- PAF acetyl-hydrolase in localized juvenile periodontitis
Role of the enzyme PAF-AH in IgG2 production in EOP
One of the “inflammatory mediators” cited above that is under investigation is “platelet activating factor,” or PAF. Our studies show that PAF may be a critical molecule for regulating IgG2 production in LJP with high levels of PAF stimulating immune cells to produce more IgG2. High levels of PAF could be caused by decreased breakdown of this molecule; this is mediated by an enzyme that is abbreviated PAF-AH. Our data indicate that LJP patients make less PAF-AH so they would have less breakdown of PAF which would cause their cells to make more IgG2 due to higher levels of available PAF. This project is aimed at discovering how and why the PAF-AH enzyme in LJP patients is less active. It also focuses on dendritic cells’ PAF-AH activity, because we have observed that such cells appear to be more common in the circulation of LJP patients.
Project director: Suzanne Barbour, Ph.D., Department of Microbiology and Immunology, VCU School of Medicine
- Human antibody reactivity to phosphorylcholine: Modulation of PAF-dependent
biological activities, induction by phosphoryl choline-bearing plaque bacteria,
and relationship to periodontal destruction
Studies of phosphorylcholine (PC) on oral bacteria and antibody to PC role in periodontal pathology
Phosphorylcholine is a small molecule present on some bacteria, and patients with periodontal diseases have higher levels of antibody (particularly IgG2 antibody) in their serum that reacts with PC. This project examines the function of both the PC on oral bacteria and this antibody. We have found that certain oral pathogens, or disease-causing bacteria, are able to invade the cells that line the bloodstream (endothelial cells) and perhaps enter the bloodstream because of their PC. The reason they can do this is that bacterial PC looks identical to PC that is present on PAF. We are therefore studying the invasion process. Secondly, we are studying the antibodies to PC which are found in all human sera. These antibodies react with PAF, placing them into a category of molecules called “auto-antibodies,” or antibodies that react with normal constituents of the body. We are attempting to determine how these “auto-antibodies” react with normal molecules to influence immune responses such as production of IgG2. Finally, these antibodies may also be involved in other diseases such as cardiovascular disease since they also react with human-oxidized LDLs, a well-known risk factor for stroke and heart attack. We are studying how oral bacteria may promote the production of antibodies to PC, which could then react with LDLs to influence the course of cardiovascular disease.
Project director: Harvey A. Schenkein, D.D.S., Ph.D., VCU School of Dentistry