In a groundbreaking discovery, scientists from Northwestern Medicine and Brigham and Women’s Hospital have identified a molecular defect that could be a primary cause of systemic lupus erythematosus (SLE), commonly known as lupus. This chronic autoimmune disease affects over 1.5 million Americans and can lead to severe damage to multiple organs, including the kidneys, brain, and heart.
The study, published in the journal Nature, reveals that this defect promotes an imbalanced immune response, which could potentially be corrected to reverse the disease. “Up until this point, all therapy for lupus is a blunt instrument. It’s broad immunosuppression,” said Dr. Jaehyuk Choi, co-corresponding author and associate professor of dermatology at Northwestern University Feinberg School of Medicine. “By identifying a cause for this disease, we have found a potential cure that will not have the side effects of current therapies.”
Dr. Deepak Rao, co-corresponding author and assistant professor of medicine at Harvard Medical School, explained that lupus involves abnormal B cell activation and antibody production, which requires help from T cells. The research team discovered that lupus patients exhibit a dramatic imbalance in the types of T cells they generate, leading to an excess of harmful T cells and a deficiency of those necessary for cell repair.
The study also identified a protein called interferon that exacerbates this imbalance by promoting the accumulation of harmful T cells. “We have known for many years that patients with lupus have too much interferon production, yet how interferon contributes to disease has been unclear,” Rao noted. The researchers found that interferon amplifies pathological T cell-B cell interactions, further driving the disease.
One of the most promising findings is the role of the aryl hydrocarbon receptor (AHR) protein. Activation of AHR can prevent T cells from developing into disease-causing cells. “This study reveals a new potential therapeutic strategy to treat lupus,” Rao said. The team aims to use small molecule activators of AHR, specifically targeting T cells, to suppress the pathological T cell response in lupus and reprogram these cells toward benign or protective functions.
This targeted approach could be safer and more effective than current broad immunosuppressive therapies, according to Dr. Choi. “While we don’t know which patients this can best help, our data suggests it could potentially be broadly useful for all patients with lupus,” he added.
Dr. Mara Lennard Richard from the Lupus Research Alliance expressed optimism about the findings, stating that the research provides hope for those struggling with lupus symptoms. However, she emphasized that lupus is a highly complex disease with many contributing factors, and more research is needed to confirm these results.
Dr. Brooke Goldner, a California-based physician and creator of the Hyper-Nourishing Nutrition Protocol for Lupus Reversal, highlighted the potential of targeted immune therapy using T cells and B cells. She noted that while this approach is promising, the effectiveness and possible side effects of these therapies are still unknown.
The research was primarily conducted in-vitro using cells from patients, and the next steps will involve testing the activators of AHR in people to determine their effectiveness in improving lupus symptoms. Despite these challenges, the researchers remain hopeful that their discovery will lead to significant advances in lupus treatment.
Lupus is a chronic autoimmune disease where the immune system attacks healthy tissue, causing inflammation and pain. It most commonly affects the joints, skin, and major organs. Symptoms include joint pain, extreme fatigue, and a characteristic butterfly rash. The disease can run in families and is more prevalent among women and certain ethnic groups.
In addition to medication, lifestyle modifications such as an anti-inflammatory diet and stress management can help manage lupus symptoms. “The field of lifestyle medicine has shown that symptoms can be reversed long-term using lifestyle modification,” Goldner said.
This study represents a significant step forward in understanding and potentially treating lupus, offering new hope to millions of patients worldwide.