Background/Purpose: Periodontitis is an inflammation of the soft and hard tissues supporting the tooth.  Aggregatibacter actinomycetemcomitans (Aa), a gram negative bacterium, is strongly associated with the aggressive form of periodontitis, particularly in young females.  Aa and its toxins induce apoptotic cell death in immune cells and hence can modulate the mucosal immune responses.  In this study, we tested the hypothesis that an infection with Aa is associated with increased autoimmunity in lupus patients. 

Methods: Circulating antibodies to Aa are indicative of an ongoing or prior infection with the organism. Thus, serum antibodies to Aa in lupus patients and controls from the Oklahoma cohort of rheumatic disease were measured by ELISA. The lupus patients with anti-Aa antibody units higher than mean+2SD of controls were classified as positive for anti-Aa. To determine the association between anti-Aa and autoantibodies to lupus-associated antigens (dsDNA, Ro/SSA, La/SSB, Sm, RNP, Ribosomal P, and Jo-1), contingency tables were constructed and statistical significance calculated using Fisher’s exact test.  Neutrophil extracellular traps (NETs) are suspected to be the source of autoantigens in lupus. Thus, the ability of Aa to induce NETosis was tested by using bone marrow derived neutrophils from lupus-prone mice. NET formation was evaluated by staining for DNA and citrullinated histones.

Results: A significant number of lupus patients (128/534, 23.97%) were positive for anti-Aa antibodies, compared to controls (1/21; 4.76%; p=0.037). Stratification of lupus patients by race showed that African American patients had significantly higher anti-Aa antibody titers as compared to patients of Caucasian origin. However, regardless of the race, anti-Aa antibody positivity was significantly associated with higher anti-dsDNA (p=0.002).  No association was observed with other autoantibody specificities. Incubation of neutrophils with Aa readily induced NETosis.

Conclusion: This study shows that an ongoing or prior infection with the periodontogenic bacterium Aa is associated with increased anti-dsDNA in lupus patients. Our data suggests the possibility that Aa induced NETosis might be involved in the amplification of anti-dsDNA response in lupus patients. Considering that the incidence of periodontitis is higher in African Americans, our study provides a strong rationale to investigate the possible link between periodontal disease and lupus in African American patients

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibody-response-to-periodontogenic-bacterium-aggregatibacter-actinomycetemcomitans-and-lupus/