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Pachucki RJ , Corradetti C , Kohler L , Ghadiali J , Gallo PM , Nicastro L , Tursi SA , Gallucci S , Tükel Ç , Caricchio R
Persistent Bacteriuria and Antibodies recognizing Curli/eDNA complexes from E. coli are Linked to Flares in Systemic Lupus Erythematosus
Arthritis Rheumatol. 2020 Nov;72(11) :1872-1881
PMID: 32840064    PMCID: PMC7722165    URL: https://www.ncbi.nlm.nih.gov/pubmed/32840064
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Abstract
OBJECTIVES: Infections contribute to morbidity and mortality in lupus, here we asked if they might also play a role in its pathogenesis. Uropathogenic E. coli (UPEC) cause urinary tract infections (UTIs) and form biofilms, multicellular communities of bacteria that are strengthen by amyloids such as curli. We previously reported that curli naturally form complexes with DNA (curli/eDNA) and these complexes induce hallmarks of lupus disease in mouse models. METHODS: We investigated 96 SLE patients who met at least 4 SLICC criteria. We tested the presence of anti-curli/eDNA complex antibodies for both IgG and IgA subclasses. Results were compared to 54 age, sex and race matched healthy controls. We then correlated the levels of anti-curli/eDNA antibodies with clinical parameters, lupus disease status and frequency of bacteriuria. RESULTS: We found anti-curli/eDNA antibodies in SLE and controls plasma, and their levels correlated with asymptomatic persistent bacteriuria and disease flares in lupus patients. Persistent bacteriuria contained curli-producing UPEC and associated with an inflammatory phenotype. Finally, curli/eDNA complexes cross-reacted with lupus autoantigens such as dsDNA in binding autoantibodies. CONCLUSIONS: We propose that UTIs or persistent bacteriuria are environmental triggers of lupus and its flares. Antibodies against curli/eDNA could serve as a sign of systemic exposure to bacterial products in lupus.
Notes
2326-5205 Pachucki, Ryan J Corradetti, Chelsea Kohler, Lynne Ghadiali, Jay Gallo, Paul M Nicastro, Lauren Tursi, Sarah A Gallucci, Stefania Orcid: 0000-0003-4737-8003 Tükel, Çagla Caricchio, Roberto Orcid: 0000-0002-1379-1118 Journal Article United States Arthritis Rheumatol. 2020 Jun 17. doi: 10.1002/art.41400.