403 Bacterial biofilm product Curli/eDNA induces neutrophil extracellular traps and serum anti-Curli/eDNA levels correlate with bacteriuria and lupus activity

BackgroundInfections are a major contributor to lupus disease. We have previously demonstrated that bacterial amyloid curli, produced by E.coli, can accelerate disease in mouse models of lupus. Interestingly curli incorporates extracellular DNA, which in turn can be both adjuvant and a self-antigen in lupus. Uropathogenic E. coli (UPEC) is responsible for the majority of urinary tract infections in SLE. Based on our previous results, we hypothesize that exposure to UPEC triggers anti-curli/eDNA antibodies and curli/eDNA complexes can trigger the innate immune system.MethodsWe investigated 98 lupus patients who met at least 4 SLICC criteria. Results were compared to 54 age, sex and race matched healthy controls. We tested the production of anti-curli/DNA complex for both IgG and IgA subclasses. We than correlated the levels of anti-curli/DNA antibodies with clinical parameters. Finally, we treated human neutrophils with curli/eDNA complexes.ResultsWe found that curli/eDNA induces neutrophil extracellular traps in a ROS-dependent manner. Anti-curli/eDNA IgG levels were detected in lupus and controls plasma and the levels correlated with persistent bacteriuria (p<0.05) and disease flares in lupus patients. In addition, anti-dsDNA could bind to anti-curli/eDNA complexes.ConclusionsWe conclude curli/eDNA complexes can activate the innate and adaptive immune system and could be a mechanism to sustain disease in lupus.AcknowledgmentsWe thank Drs. Marc Monestier and Philip Cohen for their insightful suggestions. We also thank the generosity of the lupus patients from the Temple Lupus Program.