Background and objective: Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate beta(1)-adrenoceptors (beta(1)-AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease.
Material and methods: Flow cytometry and enzyme-linked immunosorbent assay using cell culture-adherent gingival fibroblasts and/or their purified membranes and/or a synthetic peptide corresponding to the second extracellular loop of human beta(1)-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE(2) generation and CD40 expression were also tested.
Results: Circulating immunoglobulin G (IgG) from chronic periodontal disease patients (but not from normal individuals) interacted with the fibroblast surface, activating beta(1)-AR. Atenolol or CGP 20712 (beta 1-AR antagonists) and beta(1) synthetic peptide inhibited the interaction of IgG with beta(1)-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific beta(1)-AR activation, increasing PGE(2) generation and CD40 overexpression. The corresponding affinity-purified anti-beta(1)-AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo-oxygenase.
Conclusion: This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE(2) and CD40 expression) is induced as a consequence of antibody-beta(1)-AR interaction. The PGE(2)-CD40-IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.