Background Infections 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. Finally, uropathogenic E. coli (UPEC) is responsible for the majority of urinary tract infections in SLE.

Methods 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. We 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 also correlated the levels of anti-curli/DNA antibodies with clinical parameters. Finally, we treated human neutrophils with curli/eDNA complexes.

Results We found that curli/eDNA induces neutrophil extracellular traps in a ROS 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-curli/eDNA antibodies could bind to DNA demonstrating a potential molecular mimicry mechanism in lupus. Finally IgA anti-curli/eDNA levels were higher (p<0.01) in lupus donors compared to controls.

Conclusions We conclude curli/eDNA complexes can activate the innate and adaptive immune system and could be a mechanism to sustaining disease in lupus.

Funding Source(s): NIH/NIAMS and Lupus Research Alliance