Risk for development of localized juvenile periodontitis (LJP) varies markedly among different e c groups, with blacks being roughly 15 times more likely than Caucasians to develop this disease. LJP also tends to aggregate within families, suggesting that susceptibility may be genetically-defined. To date, however, a genetic marker for LJP has not been identified. Black LJP subjects mount a strong IgG response toward A. actinomycetemcornitans, the etiologic agent of this disease, a significant proportion of the IgG response being comprised of antibodies of the IgG2 subclass. The effectiveness of these IgG2 antibodies in host defense has not been defined. Genetically- defined polymorphism of IgG Fc receptors (Fc-lambda-R) can markedly affect receptor affinity for human IgG subclasses, particularly IgG2. A principal objective of this proposal is to evaluate the relationship between Fc-lambda-R polymorphism, opsonic activities of IgG subclass antibodies to A. actinomycetemcomitans, and ethnic variations in risk for LJP. Moreover, we will examine the initial IgG subclass responses to this organism following the onset of disease. Specifically, we propose to: l. Determine if variations in the frequency of allelic polymorphism of Fc-lambda-R exist among UP subjects of diverse ethnic background. 2. Define the influence of Fc-lambda-R polymorphism upon the effectiveness of IgG subclass antibodies in LJP sera in promoting opsonization of A. actinomycetemcomitans. 3. Assess temporal changes in the IgG subclass responses to A. actinomycetemcomitans which occur during the early stages of transition from a periodontally healthy state to one of LJP. 4. Compare the IgG subclass responses of ethnically diverse LJP subjects to key antigens of A. actinomycetemcomitans. The information derived from the proposed studies will provide insight into the role of Fc-lambda-R polymorphism in defining risk for LJP among various ethnic groups, and in regulating the properties of IgG subclass antibodies to A. actinomycetemcomitans in sera of LJP subjects. Moreover, these studies will enhance our understanding of the dynamics of the IgG response to A. actinomycetemcomitans following the onset of LJP, as well as of qualitative and/or quantitative variations in the IgG response of ethnically diverse LJP subjects to this organism.
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