Antibodies Against DNA Complexes Linked to Bacteriuria and Flares in Systemic Lupus Erythematosus

Antibodies against curli DNA complexes (eDNA) may be associated with persistent bacteriuria and flares in patients with systemic lupus erythematosus (SLE), indicating a link between systemic exposure to bacterial products and increased disease severity, according to study results published in Arthritis & Rheumatology.

Investigators extracted data from the Temple Lupus Cohort, a prospective cohort of patients with SLE who received care at the Temple University Lupus Program in Philadelphia, Pennsylvania. At baseline and follow-up visits, participants who met at least 4 of the Systemic Lupus Collaborating Clinics (SLICC) criteria received physical exams and laboratory testing. Urine samples were used to assess bacteriuria levels; E coli was commonly present in patients with high bacteriuria levels. Using enzyme-linked immunosorbent assay (ELISA), plasma samples were tested for immunoglobin A (IgA) and G (IgG) antibodies against curli/eDNA complexes from E coli. Patients with SLE were age-, sex-, and race-matched with healthy control participants who received care at the same facility. The plasma and urine results were compared between the 2 groups. Disease activity was measured in patients using the SLE Disease Activity Index (SLEDAI); an SLE flare was defined as an increase of ≥3 points in SLEDAI from the prior visit.

The study cohort included 96 patients with SLE and 54 healthy control participants. Both groups of patients had varying levels of IgG antibodies against curli/eDNA complexes, suggesting that most humans have been exposed to curli-expressed enterobacterial species, regardless of health status. However, patients with SLE vs the control participants had significantly higher levels of IgA antibodies against curli/eDNA (median, 0.35 vs 0.22, respectively). In addition, patients with SLE in flare vs those in remission had significantly higher levels of anti-curli/eDNA IgG antibodies (median, 2.15 vs 1.34; mean, 2.13±0.27 vs 1.42±0.17, respectively). A majority of patients with SLE who had 2 years of consecutive urine analysis data had episodes of asymptomatic bacteriuria and 35% had persistent bacteriuria. Compared with patients with intermittent bacteriuria or who consistently tested negative for bacteriuria, those with persistent bacteriuria had higher levels of IgG against curli/eDNA complexes (median, 0.70 vs 0.46 and 0.46; mean, 0.71±0.05 vs 0.48±0.05 and 0.44±0.05, respectively).

Anti-curli/eDNA levels were found to correlate with sex; levels of IgG and IgA antibodies against curli/eDNA complexes were higher among women than men with SLE. In a series of competitive ELISA tests, curli/eDNA complexes appeared to crossreact with lupus autoantigens, including double-stranded DNA, in binding autoantibodies.

According to the researchers, higher levels of anti-curli/eDNA IgA antibodies in patients suggest that curli/eDNA may have a pathogenic role in SLE. Increased anti-curli/eDNA IgG also appeared to indicate flares in disease activity.

The small number of patients included the study limited data generalizability; further research in a larger cohort is necessary to confirm these findings.

“Together with bacteriuria and other parameters of disease activity and inflammation, an increase in anti-curli/eDNA [antibodies] may pinpoint a subgroup of patients who might benefit from antibiotic therapy as adjuvant to standard of care,” the investigators wrote.

Reference

Pachucki RJ, Corradetti C, Kohler L, et al. Persistent bacteriuria and antibodies recognizing Curli/eDNA complexes from E. coli are linked to flares in systemic lupus erythematosus [published online June 17, 2020]. Arthritis Rheumatol. doi:10.1002/art.41400