In research whose pace was significantly accelerated thanks to a 2-year, $500,000 grant from the Alliance for Lupus Research (ALR), researchers have identified a specific pattern of gene activity, or “gene expression signature,” in people who develop more severe forms of systemic lupus erythematosus (SLE, or lupus). The findings, published in the March 4, 2003 edition of the Proceedings of the National Academy of Sciences, may be used in the future to help diagnose lupus, predict the development of serious disease, and guide treatment decisions, as well as leading to development of new treatments.
Using a technique that simultaneously analyzes the activity of thousands of genes in a single blood sample, ALR investigator Timothy Behrens, MD, of the University of Minnesota and his colleagues identified about 150 genes whose level of activity differed strongly between healthy people and people with lupus. One of the most dramatic differences was seen in a group of 14 genes whose activity, or “expression” level, increases in response to interferons—a family of proteins that have potent effects on the immune system and are believed to play a role in the development of lupus.
Most striking, Dr. Behrens says, was the finding that increased expression of this particular group of interferon-responsive genes “appears to be a really good marker for the patients who are going to have the most severe type of lupus, which can involve the brain, kidney, and blood cells.” Dr. Behrens and his colleagues are now trying to figure out exactly why that is, he says.
What it means for people with lupus: Identifying unique patterns of increased or decreased gene expression that are seen in lupus patients but not in people with other diseases should lead to new and improved diagnostic tests for lupus, Dr. Behrens says. Ongoing studies of the “interferon signature” in lupus may also lead to development of new treatments that block the production of interferons or their actions on genes. Testing for specific genetic signatures in patient blood samples could help doctors identify those patients most likely to benefit from such treatments.
In addition to its continuing support for Dr. Behrens’ research, ALR recently funded two new research projects and renewed support for a third project on interferon whose goals include deciphering the role of interferons in the development of lupus and investigating whether blocking the actions of specific forms of interferon can prevent or suppress disease. “We hope that together, these studies will lead to greater understanding of where interferons fit into the picture and—most important—to the development and testing of new, more targeted and more effective therapies for this potentially devastating disease,” says ALR Scientific Director John H. Klippel, MD.
To read more on the latest in lupus research, click here to download the most recent Lupus Research Update.
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