Temple University School of Medicine researchers have discovered how infections cause lupus flares. In a study funded by the Lupus Research Institute (LRI) and the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Stefania Galluci, PhD, and her team identified a mechanism through which a specific type of infection caused by thin films of bacteria (biofilms) triggers lupus flares. The infection may manifest as urinary tract infections, ear infections, and periodontal disease. Understanding biofilms and their role in lupus progression is crucial to manage the disease.
In 2013, Galluci had received an LRI Novel Research Grant to look into how female sex hormones (estrogen) turn on cells of the immune system, particularly dendritic cells, that play a key role in lupus.
“Nine out of 10 people with lupus are women. We are testing our novel idea that female sex hormones might be the cause by triggering certain cells of the immune system to overproduce inflammation-driving chemicals known as interferons. If we are correct our work could identify new drug targets in lupus,” Galluci said in a press release.
While the team was reproducing molecules that were similar to estrogen in terms of response, Gallucci discovered that curli – a bacterial protein comparable to the one producing plaque in diseases like Alzheimer’s – triggered a very strong response. The researchers found that curli sticks to DNA, in biofilms, forming very resilient fibers that can no longer be torn apart. They also found that these fibers stimulate the immune-system to produce auto-antibodies, a hallmark of lupus.
The NIH’s NIAMS newsletter, where the 2013 investigation is reported in detail, further concludes that in lupus-prone mice, the simple exposure to biofilm components could trigger disease, and even normal mice react to curli-DNA complexes by producing auto-antibodies, albeit in lower levels.
Galluci and her team will now explore if the infections that affect the whole body – caused by bacteria that would typically co-exist on skin, gut, and respiratory tract, among others – can be behind the onset of lupus and cause flares upon disease progression. With the 2016 Novel Research Grant, researchers now want to explore implications in the treatment and prevention of this disease.