Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus
| Autor: | Çagla Tükel, Sarah A. Tursi, Lauren K. Nicastro, Lynne Kohler, Roberto Caricchio, Stefania Gallucci, Chelsea Corradetti, Jay Ghadiali, Paul M. Gallo, Ryan J Pachucki |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Bacteriuria Immunology Disease medicine.disease_cause urologic and male genital diseases Article Pathogenesis 03 medical and health sciences Young Adult 0302 clinical medicine Rheumatology immune system diseases Escherichia coli Immunology and Allergy Medicine Humans Lupus Erythematosus Systemic skin and connective tissue diseases Autoantibodies 030203 arthritis & rheumatology Lupus erythematosus Systemic lupus erythematosus biology business.industry Autoantibody Middle Aged medicine.disease female genital diseases and pregnancy complications 030104 developmental biology Antibodies Antinuclear biology.protein Female Antibody business |
| Zdroj: | Arthritis Rheumatol |
| ISSN: | 2326-5205 |
| Popis: | Objective Infections contribute to morbidity and mortality in systemic lupus erythematosus (SLE). Uropathogenic Escherichia coli (UPEC) are known to trigger urinary tract infections (UTIs) and form biofilms, which are multicellular communities of bacteria that are strengthened by amyloids such as curli. We previously reported that curli naturally form complexes with bacterial extracellular DNA (eDNA), and these curli/eDNA complexes induce hallmark features of lupus in mouse models. The present study was undertaken to investigate whether anti-curli/eDNA complex antibodies play a role in the pathogenesis of SLE or development of flares in SLE. Methods In total, 96 SLE patients who met at least 4 Systemic Lupus International Collaborating Clinics disease criteria were investigated. Anti-curli/eDNA complex antibodies in the plasma were tested for both IgG and IgA subclasses. Results were compared to that in 54 age-, sex-, and race/ethnicity-matched healthy controls. Correlations of the levels of anti-curli/eDNA antibodies with clinical parameters, lupus disease status, and frequency of bacteriuria were assessed. Results Anti-curli/eDNA antibodies were detected in the plasma of SLE patients and healthy controls, and their levels correlated with the presence of asymptomatic persistent bacteriuria and occurrence of disease flares in lupus patients. Persistent bacteriuria contained curli-producing UPEC, and this was associated with an inflammatory phenotype. Finally, curli/eDNA complexes cross-reacted with lupus autoantigens, such as double-stranded DNA, in binding autoantibodies. Conclusion These results suggest that UTIs and 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 SLE. |
| Databáze: | OpenAIRE |
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