Researchers from Northwestern Medicine and Brigham and Women’s Hospital have identified a molecular defect that may be responsible for driving the autoimmune response in systemic lupus erythematosus (SLE). This discovery could pave the way for more targeted and effective treatments for the disease, they say.
The study, published in Nature, found that insufficient activation of the aryl hydrocarbon receptor (AHR) pathway leads to an overproduction of T peripheral helper cells, which in turn promote the creation of disease-causing autoantibodies. By reintroducing AHR-activating molecules to blood samples from lupus patients, the researchers were able to reprogram these detrimental cells into potentially beneficial Th22 cells that may promote healing from the damage caused by this autoimmune disease.
“Up until this point, all therapy for lupus is a blunt instrument. It’s broad immunosuppression,” co-corresponding author Jaehyuk Choi, MD, PhD, associate professor of dermatology at Northwestern University in Evanston, Ill. and co-corresponding author of the study said in a press release. “By identifying a cause for this disease, we have found a potential cure that will not have the side effects of current therapies.”
The researchers determined this finding offers two potential avenues for intervention: activating the AHR pathway with small molecule activators or reducing the excessive interferon levels in patients’ blood. In the study, both methods showed promise in decreasing the number of disease-causing cells.
This research marks a departure from present lupus treatments, which often compromise the ability of patients to fight infections. Deepak Rao, MD, PhD, co-corresponding author, assistant professor at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston, said: “We’ve identified a fundamental imbalance in the immune responses that patients with lupus make, and we’ve defined specific mediators that can correct this imbalance to dampen the pathologic autoimmune response.”
While these findings are promising, the researchers report that more work is needed to translate this discovery into clinical treatments. They are currently exploring safe and effective methods to deliver these therapeutic molecules to lupus patients.
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