Scientists at Northwestern Medicine and Brigham and Women’s Hospital have made a groundbreaking discovery in the field of lupus research. The team has identified a molecular defect that drives the pathologic immune response in systemic lupus erythematosus, commonly known as lupus. Their findings, published in the prestigious journal Nature, suggest that reversing this defect could potentially lead to a reversal of the disease.
Lupus is a chronic autoimmune disease that affects over 1.5 million people in the United States. Despite its prevalence, the underlying causes of lupus have remained elusive until now. The disease can cause severe damage to vital organs such as the kidneys, brain, and heart. Current treatments for lupus often fall short in controlling the disease and can have unintended consequences, such as weakening the immune system’s ability to combat infections.
Co-corresponding author Jaehyuk Choi, MD, PhD, a distinguished dermatologist at Northwestern Medicine, emphasized the limitations of existing lupus therapies, describing them as ‘broad immunosuppression.’ The team’s identification of a specific cause for lupus offers a potential cure that could mitigate the side effects associated with current treatments.
Dr. Deepak Rao, MD, PhD, an expert in rheumatology at Brigham and Women’s Hospital and Harvard Medical School, highlighted the team’s discovery of an immune response imbalance in lupus patients. By pinpointing key mediators that can correct this imbalance, the researchers aim to suppress the pathologic autoimmune response that characterizes lupus.
The study unveiled a novel pathway implicated in driving lupus disease progression. Analysis of blood samples from lupus patients revealed disease-related alterations in multiple molecules. These changes culminate in the inadequate activation of the aryl hydrocarbon receptor (AHR) pathway, responsible for regulating cells’ responses to various stimuli, including environmental pollutants, bacteria, and metabolites. Insufficient AHR activation leads to an overabundance of T peripheral helper cells, which in turn stimulate the production of autoantibodies that contribute to disease development.
To demonstrate the therapeutic potential of their discovery, the researchers reintroduced aryl hydrocarbon receptor-activating molecules to blood samples from lupus patients. This intervention appeared to reprogram the disease-promoting cells into a different cell type known as Th22 cells, offering a promising avenue for future treatments.
