Breakthrough in Identifying Lupus Genes

Findings could help lead to development of genetic tests to improve lupus diagnosis

Dr. Lindsey Criswell

In an unprecedented scientific leap forward, at least 12 new genes have been identified that play important roles in lupus. UCSF genetic epidemiologist and rheumatologist Dr. Lindsey Criswell, who is supported by the Rosalind Russell Medical Research Center for Arthritis, has played a major role in this research.

"The discovery of this many new genes related to lupus has certainly never happened before and the success surpassed everyone's expectations, especially given the fact that the number of patients included in these recent studies was relatively small," says Dr. Criswell, who holds the Kenneth H. Fye Endowed Chair in Rheumatology.

According to Dr. Criswell, this noteworthy achievement is the result of new technology that makes it possible to rapidly screen genetic markers across the complete set of human chromosomes, or genome, among patient volunteers to find genetic variations that increase the risk of disease.

What is most important about this advance, says Dr. Criswell, is that it reveals the biological pathways—or series of actions among proteins that turn immune cells on or off—that are critical in lupus. "Now scientists can focus on genes and pathways that we know influence who gets the disease and how severe it is likely to be," she says. "Previously we were kind of guessing on the basis of hypotheses, but now we have proof that certain genes within specific pathways are important."

Another striking aspect of the results, according to Dr. Criswell, is that many of the genes associated with lupus have been shown by other scientists to be associated with other autoimmune diseases such as rheumatoid arthritis, psoriasis or Crohn's disease. "We are finding that many of these top genes are relevant to multiple autoimmune diseases," she says. This adds evidence to the theory that a diverse range of autoimmune diseases share underlying mechanisms and may respond to similar drugs.

Also, the identification of new genes associated with lupus could hasten the day when genetic testing can aid physicians in the management of this potentially life-threatening disease. "Five years from now might be when we've identified say the 30 or 50 gene variants that are most important in terms of risk for the disease," says Dr. Criswell. A genetic screening test could then be developed to determine, for example, if relatives of a lupus patient are at significantly increased risk for the disease. Such a test could also be used when patients initially develops symptoms to determine whether they are likely to have a mild or severe form of the disease. If severe, aggressive treatment would probably be advised.

In addition, says Dr. Criswell, "Finding the new genes allows laboratory scientists to focus drug development efforts in ways that are much more likely to be productive and successful because we're pinpointing the underlying genes that are responsible for the disease. It's a very exciting time."

"The discovery of this many new genes related to lupus has certainly never happened before."
--- Dr. Lindsey Criswell

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