Scientists Discover New Genetic Immune Disorder in Children
Your immune system plays an important function in your health—it protects you against viruses, bacteria, and other toxins that can cause disease. In autoinflammatory diseases, however, the immune system goes awry, causing unprovoked and dangerous inflammation. Now, researchers have discovered a new autoinflammatory syndrome, a rare genetic condition that affects children around the time of birth.
Balintfy: The body's immune system defends against harmful influences from the outside, whether they be viral or bacterial infections, or any other form of danger.
Goldbach-Mansky: Autoinflammatory and autoimmune diseases are both disease a rheumatologist treats, and they are both diseases caused by a disregulation of the immune system.
Balintfy: Dr. Raphaela Goldbach-Mansky, a researcher at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, writes in a recent issue of the New England Journal of Medicine about a newly discovered autoinflammatory syndrome.
Goldbach-Mansky: We identified a novel disease that occurs in children at the time they are born, and is life-threatening, particularly in the early months of life.
Balintfy: She explains that the immune system has two arms. One is innate: we are born with it, and it doesn't change much. The other is adaptive: it's acquired, and gets fine-tuned as we live.
Goldbach-Mansky: Autoimmune diseases are actually caused by diseases in the adaptive immune system, the one that needs to be fine-tuned as we grow up, and also many of those develop later in life when we are older. A number of the auto-inflammatory diseases are caused by genetic mutation in the innate—in the inherited form, or hardwired form, of the immune system, the innate immune system—and many children actually present very early in life with such disorders.
Balintfy: Children with the newly discovered disorder display several serious and potentially fatal symptoms. They include swelling of bone and connective tissue; bone pain and deformity; and a rash that can cover most of the patient's body.
Goldbach-Mansky: The disease is caused by a genetic mutation in one of the innate immune system genes that actually lead to the fact that this protein is not expressed. We call the diseases DIRA—deficiency of the IL-1 receptor antagonist. And the protein, IL-1 receptor antagonist—it has a very long name—is actually a break in the immune system.
Balintfy: The disorder is rare. Scientists have identified nine patients from six families with DIRA in the Canadian province of Newfoundland, the Netherlands, Lebanon, and Puerto Rico. Dr. Goldbach-Mansky points out that now genetic testing for the disease can be developed.
Goldbach-Mansky: And in populations where we have seen those children, and particularly in Puerto Rico where the disease might actually be in certain areas quite frequent, could be identified before the children are born; and in addition there is very effective treatment available to those children.
Balintfy: Dr. Goldbach-Mansky says blocking the IL-1 pathway with anakinra, a drug that is normally used for rheumatoid arthritis, is very effective.
Goldbach-Mansky: It has to be given by daily injection, but there are other longer-acting IL-1 blocking agents that are being developed that might be effective, and I am in fact interested in testing one of such agents in those patients.
Balintfy: 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. Dr. Goldbach-Mansky says that 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. For more information on DIRA and this study, visit www.niams.nih.gov. This is Joe Balintfy, National Institutes of Health, Bethesda, Maryland.
About This Audio Report
Reporter: Joe Balintfy
Sound Bite: Dr. Raphaela Goldbach-Mansky
Topic: immune system, autoinflamatory disease, autoimmune disease, genetic disorder