IADR Abstract Archives
IgG in Anticardiolipin-Containing Sera From Periodontitis Subjects Activate TLR4
Objectives: Anticardiolipin autoantibodies (aCL), which are strongly associated with pregnancy loss in patients with the antiphospholipid syndrome (APS), are present in 15-20% of patients with chronic or aggressive periodontitis. In periodontitis, they are likely cross-reactive antibodies induced by periodontal pathogens such as P. gingivalis, A. actinomycetemcomitans, and T. denticola, all of which have peptide sequences homologous to the antibody binding site of aCL on its target antigen β2GPI. Studies of autoimmune aCL from patients with APS have implicated toll-like receptor (TLR) activation by aCL, including TLR2 and TLR4, in promotion of inflammation in the fetal tissues. We therefore hypothesized that periodontal pathogen-induced aCL, which induce fetal loss in mice, can activate TLR’s.
Methods: We tested the ability of IgG samples, with or without elevated aCL, from periodontitis subjects for their ability to induce fetal loss in mice, We further examined TLR2 and TLR4 activation in TLR-transfected HEK-Blue cells and in a trophoblastic cells line (HTR8).
Results: The results showed that aCL-positive IgG samples induced fetal resorption in 38% of fetuses, while a-CL negative samples induce only 10% fetal resorption (p=0.0003). Using HEK-blue-TLR2 and –TLR4 transfected cell lines, we found that TLR2 was not activated by IgG from periodontitis patients. However, IgG from 8 subjects testing positive for aCL activated TLR4 while IgG from subjects with or without periodontitis testing negative for aCL did not. Further, immunoabsorption of aCL significantly reduced IgG-mediated TLR4 activation. Finally, using HTR8 trophoblastic cells, we found that IL-6 and IL-8 production were stimulated by aCL-positive IgG samples; activation was completely inhibited by anti-human TLR4 monoclonal antibodies.
Conclusions: This series of experiments demonstrate that IgG antibodies found in sera in a subset of patients with aggressive or chronic periodontitis with elevated aCL can activate TLR4 and may be expected to promote inflammation at sites distant from the oral cavity.
Methods: We tested the ability of IgG samples, with or without elevated aCL, from periodontitis subjects for their ability to induce fetal loss in mice, We further examined TLR2 and TLR4 activation in TLR-transfected HEK-Blue cells and in a trophoblastic cells line (HTR8).
Results: The results showed that aCL-positive IgG samples induced fetal resorption in 38% of fetuses, while a-CL negative samples induce only 10% fetal resorption (p=0.0003). Using HEK-blue-TLR2 and –TLR4 transfected cell lines, we found that TLR2 was not activated by IgG from periodontitis patients. However, IgG from 8 subjects testing positive for aCL activated TLR4 while IgG from subjects with or without periodontitis testing negative for aCL did not. Further, immunoabsorption of aCL significantly reduced IgG-mediated TLR4 activation. Finally, using HTR8 trophoblastic cells, we found that IL-6 and IL-8 production were stimulated by aCL-positive IgG samples; activation was completely inhibited by anti-human TLR4 monoclonal antibodies.
Conclusions: This series of experiments demonstrate that IgG antibodies found in sera in a subset of patients with aggressive or chronic periodontitis with elevated aCL can activate TLR4 and may be expected to promote inflammation at sites distant from the oral cavity.