A potential link between immune response to a periodontal bacterium, Aggregatibacter actinomycetemcomintans and Systemic Lupus Erythematosus

Abstract

Abstract Infections are a significant cause of morbidity in Systemic Lupus Erythematosus (SLE). Although oral health is considerably compromised in SLE patients, the role of oral pathogens in influencing lupus pathogenesis is not known. In the present study, antibody responses to a periodontogenic, facultative anaerobic bacterium, Aggregatibacter actinomycetemcomitans (Aa), (which serve as an indicator of past or ongoing infection with Aa), were measured in SLE patients (n=587) and healthy controls (n=75). The associations between anti-Aa antibody titers and clinical measures of SLE were evaluated. The effect of Aa infection on development of lupus was investigated in the NZM2328 mice. The ability of Aa to induce neutrophil extracellular traps (NETs) was studied in vitro. Both SLE patients and controls showed the presence of anti-Aa. In SLE patients, the anti-Aa titers correlated strongly with anti-dsDNA, anti-chromatin, anti-RNP, and anti-Sm; but not with anti-Ro52, anti-Ro60, and anti-La antibodies. NZM2328 mice developed a robust immune response to Aa, and the Aa infection caused an accelerated onset of autoantibody and renal disease. In addition, Aa readily induced NETosis in NZM2328 neutrophils. Our data suggest for the first time that SLE patients are exposed to oral pathogen Aa, and this exposure significantly influences immune responses against a subset of lupus-associated autoantigens, possibly through NETosis. Furthermore, our studies suggest that management of oral health in SLE patients might prove to be beneficial for controlling lupus.