Treponema denticola enolase contributes to the production of antibodies against ENO1 but not to the progression of periodontitis

Abstract

Autoantibodies against alpha-enolase (ENO1) are often detected in various infectious and autoimmune diseases. Anti-ENO1 antibody titers were reported to be associated with the severity of periodontitis in patients with rheumatoid arthritis. Because the enolase of the periodontal pathogen Treponema denticola (TdEno) has the highest homology with ENO1 among the enolases of human-associated bacteria, we hypothesized that anti-ENO1 autoantibodies produced during the immune response to TdEno may contribute to the progression of periodontitis and tested it in human and mouse systems. In human subjects with healthy periodontium or chronic periodontitis, a strong positive correlation between the levels of anti-TdEno and anti-ENO1 antibodies was observed. In addition, the purified anti-TdEno antibodies recognized ENO1 as well as TdEno in a dot blot, confirming the cross-reactivity between TdEno and ENO1. However, anti-ENO1 antibody titers were not associated with the severity of periodontitis. To further investigate the role of TdEno in the production of anti-ENO1 antibodies and the progression of periodontitis, mice received an oral gavage of P. gingivalis alone, subcutaneous immunization with TdEno alone, or both P. gingivalis oral gavage and TdEno immunization. Immunization with TdEno induced not only anti-TdEno but also anti-mouse Eno1 (mEno1) antibodies and increased the expression of TNFα in the gingival tissues. However, alveolar bone loss was not increased by TdEno immunization. In conclusion, autoreactive anti-ENO1/mEno1 antibodies that are produced as byproducts during the antibody response to TdEno play a minimal role in the progression of periodontitis in the absence of rheumatoid arthritis.

A murine periodontitis model using coaggregation between human pathogens and a predominant mouse oral commensal bacterium

“…After blocking with 1% bovine serum albumin in PBS, the plates were incubated with saliva (1:20 dilution) or sera (1:100 dilution for immunoglobulin A [IgA] and 1:500 dilution for IgG). The remaining procedures were performed as previously described [ 13 ]. For the standard, 2 columns in each plate were coated with serially diluted (50 ng/mL to 1.56 ng/mL) mouse IgG1 (BD Diagnostic Systems) or IgA (BD Diagnostic Systems) instead of the antigen.…”

A cohort study: The Association Between Autoimmune Disorders and Leptospirosis

“…A high frequency of Borrelia burgdorfeii infections complicating autoimmune symptom, especially arthritis, has been reported previously 24 . Treponema denticola causes periodontitis and induces RA 25 . The other type of spiral bacteria-Campylobacter jejuni has also been reported to be associated with an autoimmune post-infectious polyradiculoneuropathy called Guillain Barre Syndrome 26 .…”

The role of bacterial infections in rheumatoid arthritis development and novel therapeutic interventions: Focus on oral infections

“…It is also served as a plasminogen‐binding receptor, which assists in inflammatory cell invasion 67 . Interaction between anti‐ Eno antibodies and Eno‐positive cells that express in synovial fluid and peripheral blood mononuclear cells may contribute to the elevated TNFα serum levels in patients with RA, and the circulating TNFα may contribute to the progression of periodontal disease 68,69 . In addition, P. gingivalis , T. forsythia , F. nucleatum , and A. actinomycetemcomitans contain human Eno‐homologous proteins 70 …”

“…67 Interaction between anti-Eno antibodies and Eno-positive cells that express in synovial fluid and peripheral blood mononuclear cells may contribute to the elevated TNFα serum levels in patients with RA, and the circulating TNFα may contribute to the progression of periodontal disease. 68,69 In addition, P. gingivalis, T. forsythia, F. nucleatum, and A. actinomycetemcomitans contain human Eno-homologous proteins. 70 Filifactor alocis is a Gram-positive anaerobic bacterium and has been detected in endodontic infections, and periodontal disease.…”