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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE010041-04
Application #
2131020
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1992-08-01
Project End
1999-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Dentistry
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Fu, Yali; Korostoff, Jonathan M; Fine, Daniel H et al. (2002) Fc gamma receptor genes as risk markers for localized aggressive periodontitis in African-Americans. J Periodontol 73:517-23
Kawai, T; Eisen-Lev, R; Seki, M et al. (2000) Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease. J Immunol 164:2102-9
van Schie, R C; Wilson, M E (2000) Evaluation of human FcgammaRIIA (CD32) and FcgammaRIIIB (CD16) polymorphisms in Caucasians and African-Americans using salivary DNA. Clin Diagn Lab Immunol 7:676-81
Komatsuzawa, H; Kawai, T; Wilson, M E et al. (1999) Cloning of the gene encoding the Actinobacillus actinomycetemcomitans serotype b OmpA-like outer membrane protein. Infect Immun 67:942-5
Bernstein, J M; Bronson, P M; Wilson, M E (1997) Immunoglobulin G subclass response to major outer membrane proteins of nontypable Haemophilus influenzae in children with acute otitis media. Otolaryngol Head Neck Surg 116:363-71
van Schie, R C; Wilson, M E (1997) Saliva: a convenient source of DNA for analysis of bi-allelic polymorphisms of Fc gamma receptor IIA (CD32) and Fc gamma receptor IIIB (CD16). J Immunol Methods 208:91-101
Wilson, M E; Bronson, P M (1997) Opsonization of Actinobacillus actinomycetemcomitans by immunoglobulin G antibodies to the O polysaccharide of lipopolysaccharide. Infect Immun 65:4690-5
Perry, M B; MacLean, L L; Gmur, R et al. (1996) Characterization of the O-polysaccharide structure of lipopolysaccharide from Actinobacillus actinomycetemcomitans serotype b. Infect Immun 64:1215-9
Califano, J V; Gunsolley, J C; Nakashima, K et al. (1996) Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b) lipopolysaccharide on severity of generalized early-onset periodontitis. Infect Immun 64:3908-10
Wilson, M E; Bronson, P M; Hamilton, R G (1995) Immunoglobulin G2 antibodies promote neutrophil killing of Actinobacillus actinomycetemcomitans. Infect Immun 63:1070-5

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