Molecular and Cellular Aspects of the Humoral Immune Response in Periodontal Diseases and Other Related Conditions

The aims of this study fall under four broad headings. The first was to follow up previous work in this laboratory which had indicated that local disease status is related to levels of specific immunoglobulin. A previous study had shown that gingivitis and periodontitis sites can be distinguished in that the latter have lower antibody levels to P. gingivalis in the GCF than the former, perhaps indicating local degradation by oral pathogens. In the present study, the experimental design was modified to allow matching of gingivitis and periodontitis sites within the same patient, generating the potential for a more powerful statistical analysis. Reports demonstrating differences in specific humoral immunity with ageing prompted an experimental gingivitis study on periodontally healthy young and old subjects, to investigate possible differences in local immune and inflammmatory parameters. Since chronic periodontal disease is primarily a disease of ageing, any immune deficiencies contributing to periodontal disease may be related to the ageing process itself. A previous report from this laboratory had suggested that there may be differences in immune and inflammatory processes at matched oral implant and natural tooth sites in the same patient. Part of this study, therefore, was to follow up these investigations. The second aim was to investigate local production of immunoglobulins by plasma cells in the gingiva. Therefore, separate investigations quantified the proportions of kappa and lambda light-chain producing plasma cells and also IgG and IgA subclass-producing plasma cells in the gingiva and related these to levels of the immunoglobulins in the GCF. Previous work in this laboratory has demonstrated the significance of specific serum antibody avidity to periodontal diagnosis and prognosis. Therefore, the third aim of this study was to investigate the impact of antibody avidity on the outcome of periodontal treatment. A preliminary study was set up to assess these effects; also attempting to relate microbiological parameters. A larger study was then conducted in which patients were assigned to seropositivity groups at baseline. They were then followed longitudinally to assess differences in treatment outcome. A fourth aim of this study was to look at the wider significance of immunological parameters in disease pathology. Both periodontal disease and pregnancy can in some ways be seen as a model immune-inflammatory processes. Therefore, the relevance of serum levels of IgG subclasses to pregnancy outcome was assessed. Thus the overall aim of this project was to increase understanding of the immunological aetiology of periodontal disease at local and systemic, cellular and molecular levels; and to put these findings into the wider context of immune-inflammatory processes. Confirmation of the immunological difference between gingivitis and periodontitis sites was achieved. Similarly, local humoral immune and inflammatory reactions were found to differ in older and younger individuals in that the former had lower IgG1, IgG4 and lactoferrin levels than the latter. Rates of local antibody production for matched teeth and implants were found not to correlate suggesting differences in the plasma cell infiltrate. A predominance of kappa light chain positive cells was found among plasma cells in inflamed gingival tissues. The kappa/lambda ratio of inflamed sites could be a useful method of distinguishing the stage or activity of periodontitis lesions and may differ between different forms of periodontitis. The levels of IgG subclasses in the gingival crevicular fluid were found to correlate with levels of production by local plasma cells. However, levels of local IgA1 were much lower than plasma cell numbers would indicate, suggesting degradation by bacterial proteases. This was further indicated by high levels of IgA1 fragments. The studies of periodontal treatment effects indicated that treatment outcome was predicated on initial serostatus to periodontal pathogens, and that increases in antibody avidity only occurred in patients who were initially seropositive. The studies of obstetric immunology showed that levels of IgG subclasses were significantly increased during the first trimester of normal pregnancy, but this increase did not occur in women who had spontaneous abortion. In conclusion, this project has confirmed the findings of earlier work in this laboratory, produced new findings on ageing effects, treatment effects and plasma cell infiltration in periodontal disease, elucidated further the immunology of pregnancy, and established areas for further research