The primary etiologic factor of periodontitis is bacterial plaque biofilm. Nevertheless, the factors that determine the progression of periodontitis are complex and poorly understood. Hence, the potential involvement of autoimmunity in the pathogenesis of periodontitis has been considered intermittently for years. The basic hypothesis for this PhD was that autoimmunity to native and/or posttranslationally modified periodontal extracellular matrix proteins is involved in the progression of periodontitis. Objectives The main objective of the study was to extend the understanding of periodontal disease pathogenesis beyond the common bacterial etiology and to address the hypothesis that periodontal disease is an auto-immune disease. This research will try to identify the exact neoepitope. Specific aims (i). To investigate the involvement of autoimmune reactivity towards native collagen type I (CI) and collagen type III (CIII), as well as CI and CIII posttranslationally modified by reactive oxygen specious (ROS) known to present in the inflamed tissue, ROS-CI and ROS-CIII, respectively. (ii). Develop human antibody fragment(s) specific to CI, ROS-CI, CIII and ROSCIII for diagnostic application. Methods Modification of CI or CIII was confirmed by SGS-PAGE, Capillary Electrophoresis and 3D-fluorescence. The presence of autoantibodies to ROS-CI and ROS-CIII in sera and saliva were then studied by ELISA and Western blotting using sera and saliva from individuals with Aggressive Periodontitis (AgP), Chronic Periodontitis (CP) and Gingivitis (G). Antibodies specific to ROS-CI and ROS-CIII were developed using phage display semi-synthetic human single chain fragment variable (scFv) libraries. Results Autoantibodies to native CI, native CIII, ROS-CI and ROS-CIII were observed exclusively in patients with AgP. Human antibody fragments specific to native and ROS-CI were developed and evaluated. Conclusions A. Autoimmune reactions to native and post-translationally modified self antigens may play a role specifically in the pathogenesis of AgP. B. Anti-ROS scFv specific to ROS-CI and ROS-CIII may have diagnostic future applications.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:566644 |
| Date | January 2012 |
| Creators | Hendler, Assi |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://qmro.qmul.ac.uk/xmlui/handle/123456789/3344 |
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