The basis of the proposal is a detailed examination of host- parasite interactions related to the mechanism of disease is patients infected with A. actinomycetemcomitans (Aa). The significance of the proposal is that humoral aspects of the immune response to be studied may provide an important host interface between the microorganism and manifestations of disease. To fully identify the specificity of the host responses to possible virulence factors of Aa, it will first be necessary to develop the methodology to characterize cell surface antigen preparations from the three serotypes of Aa, as well as methods for detailed analysis of human antibody responses to the individual antigens. Patients to be included in the studies will be those with evidence of periodontal disease and elevated systemic antibody responses to Aa. Studies of the antigenic specificities of the patients' antibody responses will be accomplished utilizing Western immunoblotting techniques. Initial cross-sectional studies of host responses will include IgG, IgM, IgA and IgE isotype antibodies, and the subclasses of IgG (IgGl, IgG2, IgG3, IgG4). The host response will be classified according to qualitative aspects of antigen specificities in each individual, as well as quantitative. definition of the level of response to each antigen in the preparations. Since it has been suggested that periodontal disease progresses by exacerbations and remissions, longitudinal measurements of host responses prior to, during and after the acute episodes will be examined. Recognizing that periodontal disease appears to be predominantly a disease localized to particular sites at any one time, further aims of the proposal will delineate the characteristics of the local antibody response. These analyses will include both cross-sectional studies of sites within a patient, as well as between patients and examination of longitudinal changes in antibody to Aa antigens at disease active and inactive sites, pre- and post-treatment. The responses in each study will then be compared to clinical parameters of disease and the antigenic burden of A. actinomycetemcomitans in the subgingival plaque in each patient. The results from these studies should provide a base of knowledge of the local and systemic antibody response to this proposed pathogen. Comparison of these responses to the disease parameters and to infection with A. actinomycetemcomitans should aid in understanding the mechanism of host interference with the pathogenicity of this microorganism.
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