1602 Transcriptomic profiles predict response to rituximab in SLE

Abstract

Background Epidemiological studies suggest that bacterial infections promote SLE disease in predisposed individuals, but the underlying mechanisms remain unknown. We have found that a subset of SLE patients has asymptomatic bac-teriuria associated with markers of inflammation and flares, suggesting that chronic exposures to microbial products may trigger flares in lupus. Our labs have shown that the bacterial amyloid curli, expressed in multicellular commun-ities ( biofilms) by many bacteria including E. coli , plays a major role in triggering lupus autoimmunity during infec-tion. Curli amyloid/DNA complexes strongly activate dendritic cells and macrophages. When given systemically, curli/DNA complexes and infections with curli-expressing E. coli trigger production of anti-dsDNA and anti-chroma-tin autoantibodies in lupus prone mice and in wild type mice. This stimulation is diminished in TLR2 or TLR9 deficient mice, suggesting a TLR-mediated activation of innate immunity. We have now focused on the effects of curli/DNA complexes on B cells