It is clear that some periodontitis associated organisms elicit immune responses in afflicted hosts, however, the roles these responses play in the disease process have not been clearly established. Some immune mechanisms are believed to interact with periodontal pathogens and thus moderate disease while others are thought to promote pathology. We reason that studies of early onset periodontitis (EOP) where severe disease occurs rapidly and early in life may provide important insight into the role of immune mechanisms. This is supported, in part, by the fact that EOP runs in families and appears to have an important hereditary component. Recent data by us and others indicates that the vast majority of antibody reactive with Actinobacillus actinomycetemcomitans-b (Aa-b) in EOP is IgG2. The high IgG2 titers reactive with Aa-b prompted us to examine the total serum IgG2. We found that LJP patients had 30% to 40% more IgG2 than any other clinical group. Furthermore, we found that black subjects, which have a high incidence of LJP, had significantly higher serum IgG2 as compared to age and diagnosis matched white periodontitis patients. In addition, IgG2 levels were low in children and increased dramatically around puberty when we first observe signs of LJP. In short: 1) IgG2 is high in LJP, 2) IgG2 is high in blacks which ave greatest incidence of LJP and 3) IgG2 levels increase dramatically around puberty when LJP first becomes apparent. We reason that these relationships between IgG2 and periodontal disease may not be just a coincidence but may be related to important immunological differences at the genetic level and predispose to the development of periodontal disease. In addition, we found an increased level of IgG3 associated with white LJP subjects. This LJP associated IgG3 elevation differed from the IgG2 elevation not only in being limited to white subjects but also in the lack of an age effect. The major proposition being addressed in this proposal is that serum IgG2 and IgG3 levels in LJP patients are being regulated, in part, by genetic factors. Proposed experiments are designed to assess responses of LJP patients to other IgG2 dominated carbohydrate responses, the stability of the IgG subclass response at the cellular level, as well as the effect of therapy on IgG subclass levels. These approaches are important in determining whether IgG2 and IgG3 levels in LJP are the result of disease or rather are constitutive (and thus possibly genetically determined). In assessing the immunologic basis for these observations, we may uncover candidate genes amenable to testing as part of our proposed linkage analysis of EOP patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
1P50DE010703-01
Application #
3776000
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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