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New Risk Gene for Rheumatoid Arthritis and Lupus Opens Door to More Effective Treatments
Date:9/6/2007

s of STAT4 have a 60 percent increased risk, Dr. Gregersen said. Rheumatoid arthritis is a painful inflammatory condition of the joints. It is an autoimmune disease, which means the body's immune system recognizes a product in the lining of the joint as foreign and wages an attack. Patients with lupus, also an autoimmune disease, have about double the risk compared to people without this variant of STAT4.

In a companion study by Dr. Gregersen and his colleagues, STAT4 popped up as an important risk gene in a population of patients in Korea. This paper is published this month in Molecular Medicine.

One percent of people will develop rheumatoid arthritis. There are probably dozens of genes, perhaps more, involved in triggering complex diseases like rheumatoid arthritis.

"Identifying this risk gene is important because it points us in the right direction," said Dr. Gregersen, who also just completed a whole genome-wide association study of rheumatoid arthritis that will appear later this month in the NEJM. The study is online as of September 6th with an accompanying editorial. In this paper, the scientists identified another risk gene -- TRAF1-C5.

"The identification of these two new autoimmunity genes has profound significance for our understanding of these complex diseases and our ability to develop more specific diagnostic tests and therapies," said Lindsey Criswell, MD, PhD, professor of medicine at UCSF and a co-investigator on both studies.

A lot is known about the STAT4 gene and the protein it makes. STAT4 is a signaling molecule that mediates the effects of immune system cytokines such as IL12 and some types of interferon. STAT4 controls the differentiation of T- cells into TH1 cells and may contribute to the development of TH17 cells, both of which seem to have a role in maintaining chronic inflammation in the body.

Inhibiting STAT4 can prevent or ameliorate arthritis in animal models of rheumatoid arthritis, suggesting that
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SOURCE The Feinstein Institute for Medical Research
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