Northwestern MedicineScientists Discover a Cause of Lupus and a Possible Way to Reverse It

Molecular Defect Identified as Potential Lupus Driver, Opening New Treatment Avenues

Researchers from Northwestern Medicine and Brigham and Women’s Hospital have identified a molecular defect that appears to drive the pathologic immune response in systemic lupus erythematosus (SLE). The study, published in Nature, reveals that insufficient activation of the aryl hydrocarbon receptor (AHR) pathway leads to an overproduction of disease-promoting immune cells. This discovery not only uncovers the underlying mechanisms of lupus but also suggests a potential targeted approach for treatment that may avoid the broad immunosuppression associated with current therapies.

Key Points:

• Scientists identified a molecular defect promoting the pathologic immune response in lupus
• The defect involves insufficient activation of the aryl hydrocarbon receptor (AHR) pathway
• Inadequate AHR activation results in an excess of disease-promoting T peripheral helper cells
• These cells contribute to the production of disease-causing autoantibodies
• Researchers successfully reprogrammed lupus-causing cells into potentially beneficial Th22 cells in vitro
• Activating the AHR pathway or limiting excessive interferon reduced disease-causing cells
• The study suggests a potential for developing targeted lupus treatments with fewer side effects
• Current lupus treatments often involve broad immunosuppression, increasing infection risk
• Lupus affects more than 1.5 million people in the U.S.
• The disease can cause life-threatening damage to multiple organs, including kidneys, brain, and heart
• Next steps involve developing safe and effective methods to deliver AHR-activating molecules to patients

“Up until this point, all therapy for lupus is a blunt instrument. It’s broad immunosuppression. By identifying a cause for this disease, we have found a potential cure that will not have the side effects of current therapies.”
– Jaehyuk Choi, MD, PhD, Associate Professor of Dermatology, NW Medicine

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