Antibodies to Periodontal Bacteria Are Associated with Systemic Lupus Erythematosus and Autoantibody Positivity

Periodontitis has been suggested to play a role in the etiology of systemic lupus erythematosus (SLE). However, evidence remains limited, and the underlying mechanisms are unclear. <i>Porphyromonas gingivalis</i> and <i>Aggregatibacter actinomycetemcomitans</i> are strongly linked to periodontitis. Here, we evaluate the levels of circulating antibodies against these bacteria in patients with SLE and healthy controls and analyze their association with SLE-related autoantibodies. Serum IgG antibodies against <i>P. gingivalis</i>, <i>A. actinomycetemcomitans</i> leukotoxin A (LtxA), and two control bacteria (<i>Capnocytophaga ochracea</i> and <i>Escherichia coli</i>) were quantified in 223 patients with SLE and 301 healthy controls. Data was analyzed with ANCOVA and logistic regressions adjusting for age, sex, and smoking status. Exposure to <i>P. gingivalis</i> and <i>A. actinomycetemcomitans</i>, as estimated from antibody levels, was associated with SLE (Odds Ratios (ORs) = 3.0, <i>p</i> = 0.0002 and OR = 2.61, <i>p</i> = 0.0007, respectively). An additive interaction on SLE susceptibility was observed for exposure to <i>P. gingivalis</i> and smoking, with an attributable proportion due to interaction (AP) = 0.72 (95% CI = 0.41-1.02). Anti-<i>A. actinomycetemcomitans</i> LtxA antibodies were elevated in patients positive for anti-dsDNA antibodies (<i>p</i> = 0.02) and nominally increased in those positive for anti-cardiolipin antibodies (<i>p</i> = 0.06). Elevated levels of antibodies against <i>P. gingivalis</i> and <i>A. actinomycetemcomitans</i> in patients with SLE suggest a role for these bacteria, or periodontitis, in the immunopathogenesis of SLE. An additive interaction with smoking was observed for <i>P. gingivalis</i>, and <i>A. actinomycetemcomitans</i> exposure was associated with anti-DSNA antibody positivity, supporting a link between these bacteria and SLE.