SCIENTISTS DISCOVER NEW GENETIC IMMUNE DISORDER IN CHILDREN

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SCIENTISTS DISCOVER NEW GENETIC IMMUNE DISORDER IN CHILDREN

NIHPRESS

Thursday, June 4, 2009, 6:35 AM

 

U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH NIH News

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

<http://www.niams.nih.gov/>

Embargoed for Release: Wednesday, June 3, 2009, 5:00 p.m. EDT

 

CONTACT: Trish Reynolds, 301-496-8190, <e-mail:

reynoldsp2

 

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 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 diagnosis-six in all-were 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. "

 

In addition to the NIAMS, other support came from the National Cancer Institute;

the National Institute of Allergy and Infectious Diseases; the NIH Clinical

Center; the National Human Genome Research Institute; Memorial University of St.

John's, Newfoundland; the University of Iowa, Iowa City; the University of

Utrecht, Netherlands; the University of Toronto, Canada; Lund University, Malmo,

Sweden; Shafallah Medical Genetics Center, Qatar; Feinstein Institute,

Manhasset; and Erasmus Medical School, Rotterdam, Netherlands.

 

For more information about the NIAMS Intramural Clinical Research Program, visit

the NIAMS Web site at

<http://www.niams.nih.gov/research/Ongoing_Research/Branch_Lab/Clinical_Director\

>.

 

For more information about the NIAMS Genetics and Genomics Branch, visit the

NIAMS Web site at

<http://www.niams.nih.gov/Research/Ongoing_Research/Branch_Lab/Genetics_and_Geno\

mics/default.asp>

 

For more information about autoinflammatory diseases, visit the Medline Plus Web

site, a service of the NIH's National Library of Medicine, at

<http://www.medlineplus.gov>.

 

The mission of the National Institute of Arthritis and Musculoskeletal and Skin

Diseases (NIAMS), a part of the Department of Health and Human Services'

National Institutes of Health, is to support research into the causes,

treatment, and prevention of arthritis and musculoskeletal and skin diseases;

the training of basic and clinical scientists to carry out this research; and

the dissemination of information on research progress in these diseases. For

more information about NIAMS, call the information clearinghouse at 301-495-4484

or 877-22-NIAMS (toll-free call) or visit the NIAMS Web site at

<http://www.niams.nih.gov>.

 

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency

-- includes 27 Institutes and Centers and is a component of the U.S. Department

of Health and Human Services. It is the primary federal agency for conducting

and supporting basic, clinical and translational medical research, and it

investigates the causes, treatments, and cures for both common and rare

diseases. For more information about NIH and its programs, visit <www.nih.gov>.

--

Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease

with deficiency of the interleukin-1 receptor antagonist. " N Engl J Med "

2009;360:2416-27. 

 

##

 

This NIH News Release is available online at:

<http://www.nih.gov/news/health/jun2009/niams-03.htm>.

 

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