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New Batch of Lupus Genes Discovered
Date:1/21/2008

International team of researchers finds fresh suspects for autoimmune disease

MONDAY, Jan. 21 (HealthDay News) -- Researchers from around the world have pinpointed a batch of genes that can trigger lupus, a complex autoimmune disorder that has defied both a clear-cut diagnosis and a cure for decades.

"It's an important moment in autoimmune disease research," noted Dr. Noel Rose, who is director of the Johns Hopkins Center for Autoimmune Disease Research. At least 1.5 million people in the United States suffer from lupus, a disease in which the body mistakenly begins to attack itself.

The papers, three of which appear in the Jan. 20 online issue of Nature Medicine and one of which is published in the Jan. 20 online issue of the New England Journal of Medicine, identify both novel and familiar genetic suspects for lupus. The findings lend support to the theory that a "consortium" of genes are responsible for the development of lupus, said Rose, who three decades ago became one of the first researchers to connect a specific gene with an autoimmune disease.

The researchers identified several new genetic players -- ITGAM, KIAA1542, PXK and rs10798269 among them -- that raise the risk of developing lupus, and they also confirmed other genetic regions already associated with the disease. Some of the genes that had been identified previously, such as PTPN22 and STAT 4, are associated with other autoimmune diseases such a rheumatoid arthritis and type 1 diabetes, the researchers noted.

"It is exactly the thing I was dreaming about so many years ago -- that there would be common genes that would be involved in many autoimmune diseases," Rose said. It's a case of the "bad luck hypothesis," which means "you inherited all of these genes that are perfectly normal regulatory genes, and you got just too many of them, and that will bias your response this way or that way" in terms of developing the disease, Rose explained.

The discovery that many genes are involved "means we may be one step closer to better therapies in the short run -- several years as opposed to 10 years. If we can figure out what these genes are responsible for and we can alter that, we may have a major impact on the disease," said Dr. Susan Manzi, co-director of the Lupus Center for Excellence at the University of Pittsburgh and a co-author on one of the studies.

"A better understanding of why you have this disease and what's gone wrong [creates] a potential to target better therapies," she added. A greater definition of which genes are implicated in symptoms of lupus involving the brain or kidneys, for example, would allow for more accurate screening and monitoring of people at risk for lupus, she explained.

"The holy grail is for you to have a set of genes that when they are together in the right combination incur an extremely high risk" so that people at risk can be identified and vaccinated to prevent the disease, Manzi added.

Some of the papers are the result of the recent availability of new microchip technology that allows genome-wide scans, according to Dr. Carl Langefeld, co-director of the International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), which produced the discoveries reported in Nature Genetics.

Referring to some of the studies' overlap in results, Langefeld added, "The identification of the same genetic markers in different samples further strengthens our confidence in these findings."

A fifth study done by the Scripps Institute, which appeared in the Jan. 18 issue of Immunity, took an entirely different approach, focusing instead on a genetic mutation that reduces one's risk of developing lupus, Rose added.

Lupus can affect the skin, joints, lungs, blood and other organs, and lead to cardiovascular, kidney and arthritic problems, according to the Lupus Foundation of America. Women are much more likely to be struck by lupus than men, and black women are more vulnerable than white women to developing the disease.

The role that a family history of the disease plays has been known for some time, noted Dr. Robert Kimberly, principal investigator for SLEGEN. A sibling of a person with lupus has a 20 to 30 times greater likelihood of developing the condition.

Experts also say environmental factors might jumpstart the disease.

This latest research "represents an acceleration of discovery," Kimberly said. "It's not just encouraging. It has us all quite excited about what we might be able to accomplish."

More information

For more information on lupus, go to the National Institutes of Health.



SOURCES: Noel Rose, M.D., director, Johns Hopkins Center for Autoimmune Disease Research, Baltimore; Susan Manzi, M.D., co-director, Lupus Center for Excellence, University of Pittsburgh; Carl Langefeld, M.D., co-director, International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), and director, Center for Public Health Genomics, Wake Forest University, Winston-Salem, N.C.; Robert Kimberly, principal investigator, SLEGEN, professor, medicine, Division of Clinical Immunology and Rheumatology, and senior associate dean, research, University of Alabama, Birmingham; Jan. 20, 2008, Nature Genetics online; Jan. 20, 2008, New England Journal of Medicine online; Jan. 18, 2008, Immunity


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