Researchers find gene connected to Lupus

Apr 20 2006

Researchers at the University of Minnesota have identified a variant of a gene that is present in most people with lupus, a complex and chronic autoimmune disease.

While it has been suspected that lupus has genetic elements because it runs in families, this is the first time research has shown such a strong link between the presence of a particular gene variant and a lupus diagnosis.

The research was published online in Nature Genetics on April 16, 2006.

"As treatments for disease become more personalized and tailored to an individual's specific situation and genetic makeup, identifying carriers of this gene variant could be helpful in developing the most successful treatment plan," said Timothy W. Behrens, M.D., professor of medicine and co-leader on the paper.

In addition to the University of Minnesota, the research was done in partnership with scientists from Uppsala University, Sweden, and the Broad Institute of Harvard University and the Massachusetts Institute of Technology.

The researchers studied DNA samples of lupus patients and healthy people (used as controls) from the United States, Spain, Sweden, and Argentina, looking for changes in the DNA sequence of a gene known as interferon regulatory factor 5 (IRF5). They identified a DNA variant that was found more frequently in lupus patients compared with the healthy people used as controls. Further experiments showed that this single change in the DNA sequence of IRF5 altered the way that the gene is expressed in cells of the immune system.

Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease that affects multiple organs. In cases of lupus, a person's immune system attacks its own tissues, causing inflammation and symptoms including pain, fatigue, and rashes. The disease is difficult to diagnose because it mimics other diseases, making genetic discoveries like this one promising for developing better diagnostic tools as well as more effective treatments.

The gene variation Behrens and his colleagues found is common--50 percent of all people carry one copy of the gene variant and 25 percent carry two copies. Yet clearly not all people who carry the gene variant develop lupus. Behrens said this particular genetic variation is not acting alone to cause the lupus; it likely interacts with other genes as well as environmental factors to cause the disease.

The gene the researchers identified plays a role in turning on a pathway in the body's immune system that is meant to fight infection. In the case of people with lupus, this pathway is turned on and it doesn't turn off, causing the body to begin attacking its own tissue.

Further study of this gene and how it impacts the body's immune response could lead to the development of drugs that would target this pathway to treat patients who carry the gene.

Funding for the research was provided the National Institutes of Health as well as foundations, including the Lupus Foundation of Minnesota.