Duke Researchers Discover Candidate Susceptibility Gene For Autoimmune Disease

ls that had similar clinical signs, the researchers hypothesized the animals were producing too much of a potent inflammatory protein called tumor necrosis factor alpha (TNFa).
To test their idea, the researchers injected the TTP-deficient animals with an antibody that neutralizes TNFa. In a dramatic and almost complete reversal, all signs of disease completely disappeared.

The findings support preliminary results of human clinical trials being conducted at Duke and other research institutions of an experimental treatment for rheumatoid arthritis (RA) that also uses antibodies to TNFa, Blackshear said. Such studies have shown antibodies to TNFa can significantly reduce the symptoms of RA in patients.

"We know that TNFa is involved in many human inflammatory diseases including autoimmune disorders and septic shock," Blackshear said. "This finding provides insight into a new gene that appears to regulate TNFa. It is possible that defects in this gene may cause people to be susceptible to developing autoimmune diseases."

The corresponding gene has been identified in people, and Blackshear's group will soon begin a study to see if mutations in the gene correlate with autoimmune disease in people.

"The TTP-deficient mouse is an exciting new model of arthritis," said Haynes, chairman of medicine at Duke and director of the Duke University Arthritis Center. "It also provides important new information about the types of genes that can cause arthritis."

In addition to using the animal model to understand the autoimmune response, Blackshear will continue studies to determine how TTP is involved in the insulin response.

"Right now we really don't have a good handle on what TTP is doing, although there are hints it is involved in gene regulation," Blackshear said. "Our next step will be to determine if it is involved in synthesis or degradation of TNF_ and then move forward to our original question of how TTP i

Contact: Karyn Hede George
Duke University

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