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'Flap' on protein suggests new therapies for autoimmune diseases

Researchers at National Jewish Medical and Research Center who are studying a protein implicated in the development of lupus and rheumatoid arthritis have discovered a unique flap that is crucial to the proteins function. When they created a flap-free version of the molecule, it engaged receptors but triggered no biological activity. The findings, reported in the February 8 issue of Cell, provide insight into an important immune-system protein and suggest that the flap-free version may one day serve as a treatment for various autoimmune diseases.

The molecule, known variously as Tall-1, BlyS, BAFF, THANK and zTNF4, has generated intense interest in the biomedical community because of its role in both autoimmunity and the normal immune response.

Our studies have revealed the structural element crucial to Tall-1s ability to trigger maturation of B cells and antibody production, said Gongyi Zhang, Ph.D., Assistant Professor of Immunology at National Jewish. By removing Tall-1s unique flap, we have created a molecule that could have important therapeutic applications in lupus, rheumatoid arthritis
and other autoimmune diseases.

Tall-1 is an important regulator of the immune system. It spurs B cells to mature and produce antibodies, one of the bodys major defense mechanisms. Mice engineered to make too much Tall-1 develop lupus-like symptoms. People with lupus and rheumatoid arthritis have been shown to have high levels of Tall-1 in their blood.

Lupus and rheumatoid arthritis are autoimmune diseases in which the bodys immune system mistakenly attacks its own tissues. Approximately 1.4 million people in the United States, mostly women, suffer from lupus. Rheumatoid arthritis afflicts approximately 2.1 million people in the U.S.

Hong-Bing Shu, Ph.D., Assistant Professor of Immunology at National Jewish, originally identified Tall-1 in 1999 and soon thereafter one its receptors, BCMA. He collaborated with Dr. Zhang to determi
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Contact: William Allstetter
allstetterw@njc.org
303-398-1002
National Jewish Medical and Research Center
7-Feb-2002


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