August, 2020

A new study led by Dr. Roberto Caricchio, Dr. Stefania Gallucci and Dr. Cagla Tukel, funded by the Lupus Research Alliance, has shown that lupus flares are associated with high levels of antibodies against a specific bacterial protein, called curli. Published in Arthritis and Rheumatology, the study also showed that high levels of anti-curli antibodies are linked to high levels of flares and E Coli bacteria in the urine of lupus patients. The human body generally has harmless E-Coli bacteria in the gut; however, certain types of E-Coli can cause infection in other organs and produce new, harmful bacterial protein complexes.

In the current study, scientists found that a blood test for antibodies against curli complex could help identify a patient’s exposure to harmful bacteria linked to the development of lupus and lupus flares. If a lupus patient has a large amount of the curli-producing bacteria in the urine, an antibiotic treatment destroying bacteria could be helpful.

Knowing that people with lupus are susceptible to dangerous bacterial infections, Dr. Caricchio’s, Dr. Gallucci’s and Dr. Tukel’s team explored whether bacteria can affect how lupus behaves in the body. The team had previously looked in mice and found that, when exposed to E-Coli bacteria, the bacterial protein curli accelerated lupus. More specifically, the curli produced by bacteria can attach to DNA, forming a ‘curli/DNA complex,’ which stimulate immune cells and lead to inflammation, production of interferons and acceleration of lupus in mice.

Drs. Caricchio, Gallucci and Tukel wanted to then test if curli complexes also affected human lupus patients. Their current study compared the levels of antibodies against the curli complex between 96 people with lupus and 54 people without lupus, maintaining similar age, sex, and race profiles between the two groups. Interestingly, the researchers in this study discovered that human blood has antibodies, a type of immune response protein, against curli complexes. They found that lupus and non-lupus individuals had similar levels of antibodies against Curli complexes. However, people with lupus who flared had higher levels of curli complexes in their blood than those who did not flare.

Additionally, previous research has shown that a specific type of antibody called IgA is produced in slimy substances called mucus secreted throughout the body.  In this study, people with lupus had higher levels of this IgA antibody against curli complexes than people without lupus did; this finding led to the hypothesis that in people with lupus, curli complexes start with a mucosal infection caused by bacteria. After testing lupus patients, researchers found that 35 percent of patients had persistent asymptomatic bacteria in their urine over two years. Having persistent bacteria was not only linked to higher levels of anti-curli complex antibodies, but also to chronic inflammation and increased flares. Notably, women with lupus had higher levels of both blood (IgG) antibodies and IgA antibodies against curli complexes compared to men with lupus. As a result, researchers suggest that the link between bacterial curli complexes and flares is especially strong in female lupus patients.

Based on these findings, Drs. Caricchio, Gallucci and Tukel propose that the higher level of curli complexes from a bacterial mucosal infection can increase disease activity, leading to flares. As such, high levels of anti-curli complex antibodies are a result of harmful bacteria; in this case, an antibiotic treatment eliminating bacteria or the modification of the local microbiome could be beneficial in decreasing flare activity.