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.

KEYWORDS:

• Treponema denticola
• enolase
• periodontitis
• autoantibody
• TNFα

Abbreviations

RA	=	rheumatoid arthritis
ENO1	=	human enolase 1
mEno1	=	mouse enolase 1
TdEno	=	Treponema denticola enolase
PI	=	plaque index
GI	=	gingival index
BOP	=	bleeding on probing
PPD	=	probing pocket depth
CAL	=	clinical attachment level

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplementary material can be accessed here.

Additional information

Funding

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare [HI13C0016] and by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT, KOREA [NRF-2017M3A9B6062986].