Study Reveals a Way to Potentially Reverse Lupus

Researchers found a molecular defect in people with lupus that could potentially be reversed using a therapy that is unlikely to cause side effects like those associated with current treatments.

Systemic lupus erythematosus (SLE) is an autoimmune disease that impacts an estimated 1.5 million people in the United States. In people with lupus, the immune system attacks healthy tissues, leading to inflammation and tissue damage.

Some people with this condition experience mild symptoms, such as low-grade fever, joint pain, and a butterfly-shaped rash across the nose and cheeks. However, for others, the disease can severely impact the brain, heart, kidneys, and other organs.

Although lupus has no cure, medications like hydroxychloroquine and immunosuppressants can help reduce disease activity and the risk of joint and organ damage. However, hydroxychloroquine is associated with specific eye-related side effects and immunosuppressants dampen the immune system and reduce the body's ability to fight infections.

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Moreover, despite some advancements in developing new treatments for lupus, progress toward uncovering the cause of the disease has been slow.

Now, researchers from Northwestern Medicine and Brigham and Women's Hospital may have uncovered one specific cause of lupus and a treatment strategy that targets this cause — a discovery that may lead to a cure for the disease.

Scientists identify what might cause and cure lupus

In an experimental study published on July 10 in Nature, scientists discovered that lupus-related changes in molecules like cytokines and interferon circulating in the blood of people with the disease suppresses the activation of aryl hydrocarbon receptor (AHR)- controlled pathways. These pathways regulate cellular responses to environmental pollutants, metabolites, and bacteria.

Because of this insufficient activation, too many T peripheral helper cells, which promote the production of disease-causing autoantibodies, accumulate in the body, resulting in lupus symptoms.

To explore this further, the researchers added AHR-activating molecules to blood samples from people with lupus. They observed that adding activating molecules reprogrammed lupus-causing cells to act as Th22 cells, which may boost healing from lupus-related damage.

The researchers say this essentially reprograms disease-promoting cells into benign tissue repair cells.

Moreover, the researchers suggest that reversing this molecule defect is unlikely to have the side effects of current treatments as it does not suppress the immune system as a whole. Instead, it targets what the scientists believe is a root cause of lupus.

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"We found that if we either activate the AHR pathway with small molecule activators or limit the pathologically excessive interferon in the blood, we can reduce the number of these disease-causing cells," said co-corresponding author Dr. Jaehyuk Choi, M.D., Ph.D., a dermatologist at Northwestern Medicine and associate professor of dermatology at Northwestern University Feinberg School of Medicine, in a news release.

Choi adds that if these effects remain over time, this strategy may be a potential cure for lupus.

Moving forward, the research team plans to investigate how these disease-reversing molecules can be incorporated into a safe and effective therapy for individuals with lupus that would not only treat the disease but also potentially reverse it.

Choi said, if successful, these and similar next generation treatments could be available to people within a few years.

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