Autoantibodies to β1-adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E2 generation

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Abstract

Background and Objective:

Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate β1-adrenoceptors (β1-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 β1-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE2 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 β1-AR. Atenolol or CGP 20712 (beta 1-AR antagonists) and β1 synthetic peptide inhibited the interaction of IgG with β1-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific β1-AR activation, increasing PGE2 generation and CD40 overexpression. The corresponding affinity-purified anti-β1-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 (PGE2 and CD40 expression) is induced as a consequence of antibody–β1-AR interaction. The PGE2–CD40–IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.

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