Background/Purpose: Bacterial infections are a major contributor to morbidity and mortality in SLE, a known trigger of flares and they are often difficult to distinguish from lupus flares as a definitive biomarker is still lacking. Urinary tract infections (UTIs) such as those due to uropathogenic E. coli (UPEC), are characterized by the generation of a unique form of amyloid called curli. We have previously demonstrated that curli amyloid can induce or accelerate disease in mouse models of SLE. Curli can strengthen the structure of biofilms and integrate extracellular DNA, which in turn can be both adjuvant and a self-antigen in lupus patients. Curli can elicit a humoral response against themselves. Based on our previous results, we hypothesize that SLE patients can generate anti-Curli/DNA antibodies and that they correlate with flares

Methods: We investigated 34 lupus patients who met at least 4 SLICC criteria, 29 women and 5 men. 17 sex matched healthy controls were used. We developed a novel ELISA to detect anti-curli antibodies by using the curli/DNA complex as antigen. We tested IgG and IgA subclasses. We also performed competitive ELISAs to determine if curli/DNA antibodies cross reacted with classic lupus autoantibodies. Finally, we correlated the levels of anti-curli/DNA antibodies with several clinical parameters including anti-dsDNA antibodies, bacteriuria and disease flares (SLEDAI). Flares were calculated as an increase of at least 3 points in the SLEDAI from the prior visit.

Results: We found that Lupus patients and healthy controls generated anti-curli antibodies of both IgG and IgA subclasses. We also found that anti-curli antibodies recognized human chromatin but not dsDNA. Interestingly, female lupus patients had significant higher levels of anti-curli antibodies than female controls and males with lupus (p=0.047 and p=0.026 respectively). Remarkably, higher levels of anti-curli antibodies significantly correlated with the levels of anti-dsDNA antibodies (p=0.029), persistent bacteriuria (p=0.035) and lupus flares (p=0.024).

Conclusion: Taken together these results demonstrate that both healthy controls and lupus patients are exposed to curli-forming bacteria and generate systemic and mucosal immune responses (IgG and IgA subclasses) against curli. Moreover, women with SLE have much higher levels of anti-curli antibodies than men possibly due to higher rate of urinary tract infection, especially by E. coli. Since many female patients had persistent bacteriuria, bacterial colonization could be a significant pathogenic mechanism in lupus. Finally, the levels of anti-curli antibodies in lupus patients are a promising biomarker of flares.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-against-bacterial-products-curlidna-are-found-in-lupus-patients-and-are-associated-with-disease-flares/