Summary: Researchers at Northwestern Medicine and Brigham and Women’s Hospital traced lupus to too little activation of the aryl hydrocarbon receptor (AHR). That shortfall drives immune cells to make autoantibodies, which attack the body’s own tissues. Turning AHR back on in patients’ blood samples reprogrammed those cells. That gives a new target for flares that last despite the best care from chronic pain specialists.
Lupus is an autoimmune disorder marked by frequent flares and damage to many organs, despite the best treatment from chronic pain specialists. Science has struggled to find the root cause of the disease. In the new study, it appears that researchers have finally found it. They also showed how to reverse that immune defect. That gives hope that science may soon find a lupus cure.
Lupus, or systemic lupus erythematosus (SLE), is a crushing autoimmune disease. It affects over 1.5 million people in the United States alone. It can badly damage many organs, including the kidneys, brain, and heart. It causes huge suffering and badly hurts the quality of life of those who have it.
For years, the exact cause of lupus was a mystery. Not knowing the cause has made it hard to treat.
In lupus, the immune system wrongly attacks healthy tissue. That leads to inflammation and damage – it’s a kind of autoimmune disorder. People with lupus often have bouts of illness, called flares. They also have periods of remission, when symptoms ease or go away. Flares are hard to predict, and that makes lupus hard to manage.
Lupus has long been treated with broad immunosuppressants. These drugs turn down the whole immune system. They can ease symptoms, but they come with serious side effects, such as a higher risk of infections. They also fail to fully stop the disease. So organ damage goes on, causing serious, often life-threatening problems.
Organ damage in lupus can be severe. Lupus nephritis, a type of kidney inflammation, can lead to kidney failure if not well managed. When lupus reaches the brain, it can cause thinking problems, seizures, or strokes. Heart and blood vessel diseases are also more common in people with lupus.
In a new landmark study, scientists from Northwestern Medicine and Brigham and Women’s Hospital made a major leap in understanding lupus. They found a molecular defect that drives the harmful immune response in lupus. That offers hope for new treatments. The defect involves the aryl hydrocarbon receptor (AHR). This molecule controls how cells respond to pollutants, bacteria, and other substances.
The researchers found that the AHR pathway is not switched on enough in lupus patients. This leads the body to make too many immune cells. Those cells create the autoantibodies that cause the disease.
These autoantibodies attack the body’s own tissues, causing the damage seen in lupus. By finding this exact defect, the researchers have pinpointed a possible target for new therapies.
To test their discovery, the scientists added AHR-activating molecules back into blood samples from lupus patients. This step appeared to reprogram the harmful immune cells into a type that may promote healing instead of damage. This finding matters because it suggests that targeting the AHR pathway could fix the immune imbalance in lupus. It could do so without shutting down the whole immune system the way current treatments do.
This research is a major step forward in understanding and treating lupus. If the effects of AHR activation last, this approach could lead to a cure for lupus. Until now, that was hard to even imagine.
The researchers, including Dr. Jaehyuk Choi from Northwestern University and Dr. Deepak Rao from Harvard Medical School, are now working on new treatments based on their findings. Their goal is therapies that can safely and effectively switch on the AHR pathway in lupus patients.
This new direction in lupus research brings fresh hope to millions of patients and their families. They have been waiting for treatments that work better and do less harm. Pairing this breakthrough with interventional pain management in St. Louis and other care can greatly improve the quality of life for lupus patients.
Source:
Law, C., Wacleche, V. S., Cao, Y., Pillai, A., Sowerby, J., Hancock, B., Horisberger, A., Bracero, S., Skidanova, V., Li, Z., Adejoorin, I., Dillon, E., Benque, I. J., Nunez, D. P., Simmons, D. P., Keegan, J., Chen, L., Baker, T., Brohawn, P. Z., … Rao, D. A. (2024). Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus. Nature, 1–10. https://doi.org/10.1038/s41586-024-07627-2
Dr. Gurpreet Singh Padda, MD, MBA, MHP
