Bacterial Biofilm Product Curli/Edna Induces NETs and Serum Anti-Curli/Edna Levels Correlate with Bacteriuria and Lupus Activity

Ryan Pachucki¹, Chelsea Corradetti², Stefania Gallucci³, Cagla Tukel³, Sarah Tursi³, Laura Nicastro³, Lynne Kohler², Yaj Ghadiali⁴, Laurie Kilpatrick⁵ and Roberto Caricchio¹, ¹Medicine Rheumatology, Lewis Katz School of Medicine, Philadelphia, PA, ²Rheumatology, Lewis Katz School of Medicine, Philadelphia, PA, ³Microbiology and Immunology, Lewis Katz School of Medicine, Philadelphia, PA, ⁴Medicine, Lewis Katz School of Medicine, Philadelphia, PA, ⁵Temple Lung Center, Lewis Katz School of Medicine, Philadelphia, PA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoantibodies, infection and innate immunity, Lupus, Neutrophil Extracellular Traps

Session Information

Date: Tuesday, October 23, 2018

Session Title: Systemic Lupus Erythematosus – Etiology and Pathogenesis Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: 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 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 than 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. IgA anti-curli/eDNA levels were higher (p<0.01) in lupus donors compared to controls.

Conclusion:

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

Disclosure: R. Pachucki, None; C. Corradetti, None; S. Gallucci, None; C. Tukel, None; S. Tursi, None; L. Nicastro, None; L. Kohler, None; Y. Ghadiali, None; L. Kilpatrick, None; R. Caricchio, None.

To cite this abstract in AMA style:

Pachucki R, Corradetti C, Gallucci S, Tukel C, Tursi S, Nicastro L, Kohler L, Ghadiali Y, Kilpatrick L, Caricchio R. Bacterial Biofilm Product Curli/Edna Induces NETs and Serum Anti-Curli/Edna Levels Correlate with Bacteriuria and Lupus Activity [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/bacterial-biofilm-product-curli-edna-induces-nets-and-serum-anti-curli-edna-levels-correlate-with-bacteriuria-and-lupus-activity/. Accessed July 9, 2020.

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