Navigation Links
Scientists discover new genetic immune disorder in children

Your immune system plays an important function in your healthit 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 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, and other institutions have discovered a new autoinflammatory syndrome, a rare genetic condition that affects children around the time of birth. The findings appear in the current issue of the New England Journal of Medicine.

The scientists have termed the new autoinflammatory syndrome DIRA (deficiency of the interleukin-1 receptor antagonist). Children with the disorder display a constellation of serious and potentially fatal symptoms that include swelling of bone tissue; bone pain and deformity; inflammation of the periosteum (a layer of connective tissue around bone); and a rash that can span from small individual pustules to extensive pustulosis that covers most of the patient's body. Most of the children begin to have symptoms from birth to 2 weeks of age.

"The beauty of this discovery is that the symptoms of this devastating disease can now be treated," said NIAMS director and immunodermatologist, Stephen I. Katz, M.D., Ph.D. "The abnormal inflammatory pathways seen in this disease may also help us understand other common diseases that share clinical features, such as psoriasis, as well as other autoinflammatory disorders."

"We knew when we saw these children that we were dealing with a previously unrecognized autoinflammatory syndrome. The clinical characteristics were distinct from other diseases we had seen before," said NIAMS researcher and lead author Raphaela Goldbach-Mansky, M.D., M.H.S. When her colleague, Dr. Ivona Aksentijevich, tested the first patient for genetic abnormalities, their suspicions were confirmed, and ultimately abnormalities were found in a number of other cases.

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 the role of interleukin-1 in human biology and disease."


Contact: Trish Reynolds
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Related biology news :

1. UK scientists working to help cut ID theft
2. Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes
3. Comet probes reveal evidence of origin of life, scientists claim
4. Scientists link fragile X tremor/ataxia syndrome to binding protein in RNA
5. Male elephants get photo IDs from scientists
6. Scientists retrace evolution with first atomic structure of an ancient protein
7. Muscle mass: Scientists identify novel mode of transcriptional regulation during myogenesis
8. Carnegie Mellon scientists develop nanogels that enable controlled delivery of carbohydrate drugs
9. Clemson scientists shed light on molecules in living cells
10. Scientists tackle mystery mountain illness
11. T. rex quicker than Becks, say scientists
Post Your Comments:
(Date:11/17/2015)... Paris from 17 th until ... from 17 th until 19 th November ... has invented the first combined scanner in the world which scans ... Until now two different scanners were required: one for passports ... on the same surface. This innovation is an ideal solution ...
(Date:11/17/2015)... 2015  Vigilant Solutions announces today that Mr. ... Directors. --> --> ... the partnership at TPG Capital, one of the largest ... Billion in revenue.  He founded and led TPG,s Operating ... companies, from 1997 to 2013.  In his first role, ...
(Date:11/16/2015)... Nov 16, 2015  Synaptics Inc. (NASDAQ: ... solutions, today announced expansion of its TDDI product ... touch controller and display driver integration (TDDI) solutions ... These new TDDI products add to the previously-announced ... TD4302 (WQHD resolution), and TD4322 (FHD resolution) solutions. ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica Richman and ... early in their initial angel funding process. Now, they are paying it forward ... make early stage investments in the microbiome space. In this, they join ...
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... healthy metabolism. But unless it is bound to proteins, copper is also toxic ... (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study of ...
(Date:11/24/2015)... , Nov. 24, 2015  Clintrax Global, Inc., a worldwide ... Carolina , today announced that the company has set a ... a 391% quarter on quarter growth posted for Q3 of 2014 ... and Mexico , with the establishment of ... December 2015. --> United Kingdom and ...
Breaking Biology Technology: