Researchers at Northwestern Medicine, in collaboration with Brigham and Women’s Hospital, have discovered changes in multiple blood molecules that promote the pathological immune response in systemic lupus erythematosus (SLE), an autoimmune disease. This finding could pave the way for new therapeutic targets.
Lupus affects approximately 1.5 million people in the U.S., according to the Lupus Foundation of America. The disease can be life-threatening, damaging critical organs such as the kidneys, brain, and heart. Current treatments often do not effectively manage the disease and may also compromise the body’s infection-fighting capabilities.
“Until now, all lupus therapies have been broad immunosuppressants,” said co-corresponding author Jaehyuk Choi, MD, PhD, associate professor at Northwestern University Feinberg School of Medicine and dermatologist at Northwestern Medicine. “By identifying a cause for this disease, we’ve found a potential cure without the side effects of existing therapies.”
Published this week in Nature, the study uncovers a new pathway driving lupus. The team discovered that disease-associated changes in multiple blood molecules result in the insufficient activation of a pathway regulated by the aryl hydrocarbon receptor (AHR). This receptor controls how cells respond to environmental factors like pollution, bacteria, or metabolites. Insufficient AHR activation leads to an excess of T peripheral helper cells, which drive the development of autoantibodies.
“We’ve pinpointed a fundamental imbalance in the immune response in lupus patients and identified specific mediators that can correct this imbalance,” said co-corresponding author Deepak Rao, MD, assistant professor at Harvard Medical School and rheumatologist at Brigham and Women’s Hospital.
The researchers then tested whether this new understanding could aid in lupus treatment development. They found that reintroducing molecules that activate AHR to the blood appeared to reprogram lupus-causing cells into Th22 cells, which may promote healing from autoimmune damage.
“If we activate the AHR pathway with small molecule activators or limit the excess interferon in the blood, we can reduce the number of these disease-causing cells,” explained Choi. “If these effects are durable, this may offer a potential cure.”
Choi, Rao, and their team are now working on developing new lupus treatments based on this discovery, aiming to deliver these molecules safely into patients.