For the millions of people living with lupus – a chronic autoimmune disease that can damage the kidneys, brain and other vital organs – treatment options remain limited and often come with serious side effects. A $1.7 million grant from the National Institutes of Health will allow a University of Oklahoma researcher to continue investigating a protein that may help explain why the disease develops and how it might be treated more precisely.
Carol Webb, Ph.D., a professor at the OU College of Medicine, has spent her career studying the protein ARID3a. Her research has shown that people with lupus have higher numbers of B cells (a type of immune cell) containing ARID3a than healthy individuals, and patients with more of these cells tend to have more active and severe disease. In mouse research models, increasing ARID3a in B cells caused the animals to produce harmful antibodies that attacked their own tissues, similar to what is observed in lupus.
Lupus is a complicated disease in which the immune system turns against the body and can damage organs such as the kidneys and brain, making it especially challenging to study and treat. We believe these B cells may eventually help us detect disease earlier and guide the development of more effective, targeted therapies."
Carol Webb, Ph.D., Professor, OU College of Medicine
In lupus, the immune system attacks the body by mistake. Normally, young B cells – the immune cells that make antibodies – must pass an important "safety check" to make sure they do not target healthy tissue. Webb's research suggests that ARID3a may disrupt that safety system.
Her team found that in healthy people, these young B cells do not contain ARID3a. But in people with lupus, some of these young B cells do contain the protein. This finding suggests that ARID3a may allow harmful cells to slip past the body's natural protections.
With the new NIH funding, the researchers will focus on three main goals: identifying the genes directly controlled by ARID3a, understanding how the protein helps B cells break normal safety rules, and testing whether blocking ARID3a in mice can reduce lupus symptoms.
If the studies are successful, ARID3a could become both a warning sign of disease activity and a possible target for new treatments. Instead of suppressing the entire immune system, which is how many current lupus drugs work, future therapies might more precisely target the pathways that cause harm.
"In the past 60 years, the Food and Drug Administration has approved only three drugs for lupus," Webb said. "We really need a more effective treatment."
About the project
Research reported in this news release was supported by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, under award number R01AI189437. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Webb also received a bridge grant from Presbyterian Health Foundation in Oklahoma City that contributed to her earning the NIH grant.
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