All the children had inherited mutations in IL1RN, a gene that encodes a protein known as interleukin-1 receptor antagonist (IL-1Ra). IL-1Ra binds to the same cell receptors as the inflammatory protein interleukin-1, and acts as a brake on this inflammatory protein. Without IL-1Ra, the children's bodies cannot control systemic inflammation that can be caused by interleukin-1.
The scientists identified nine patients from six families with DIRA in the Canadian province of Newfoundland, the Netherlands, Lebanon, and Puerto Rico. Those who were alive at the time of diagnosissix in allwere treated with anakinra, a drug that is normally used for rheumatoid arthritis and is a synthetic form of human IL-1Ra. Although the patients were resistant to other medications such as steroids, most responded successfully and immediately to anakinra. "Our first patient had been unresponsive to several treatments, and his health care team had almost given up. But with anakinra, he was out of the hospital in 10 days and his symptoms resolved," Dr. Goldbach-Mansky said.
Although the mutation that causes DIRA is rare, as many as 2.5 percent of the population of northwest Puerto Rico are carriers. Since DIRA is recessively inherited, these data suggest that it may be present in about 1 in 6,300 births in this population. Because the mutation was found in three independent Dutch families, newborn screening for DIRA in this population, as well as that of northwest Puerto Rico, may be warranted, Dr. Goldbach-Mansky said.
"The DIRA discovery can be attributed to an innovative and collaborative effort between clinicians and laboratory researchers at NIAMS and an international team of dedicated investigators," said NIAMS Clinical Director and coauthor Daniel L. Kastner, M.D., Ph.D. "Moreover, the unveiling of this novel autoinflammatory syndrome provides us with a tool to further dissect t
|Contact: Trish Reynolds|
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases