Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify cause of Job's syndrome

21.09.2007
The rare immunodeficiency disorder known as Job’s syndrome is caused by a specific genetic mutation that both overstimulates and understimulates the human immune system, leading to harmful bacterial and fungal infections and the physical features characteristic of the syndrome, according to two independent groups of scientists, one from the National Institutes of Health (NIH) and the other from the Tokyo Medical and Dental University.

The NIH team’s report will be available the evening of September 19 online in The New England Journal of Medicine. The Tokyo group published its findings in Nature last month.

“Understanding the genetic cause of this rare immunological disorder is a signal accomplishment, revealing information that has been sought for decades,” says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), a component of NIH. "The immunological insights from this study not only promise to open new therapeutic doors for Job’s syndrome, but also provide new leads for treating other immunodeficiency diseases.”

Only about 250 cases of Job’s syndrome (pronounced like “robe,” and technically known as hyperimmunoglobulin E syndrome, or HIES) have been reported since it was first discovered in 1966. While individuals with Job’s syndrome often live long lives, life-threatening complications from basic infections are a constant concern. Identifying the specific gene implicated in the disease could benefit scientific study of several diseases that afflict people with Job’s syndrome, including infections caused by Aspergillus, Candida and Staphylococcus.

Job’s syndrome makes the immune system extremely sensitive to invading microbes. People with the syndrome often have multiple, recurring ailments, such as skin infections that cause lesions and boils, and lung infections that cause pneumonia. They also are at high risk of breaking bones, having a curved spine, and experiencing facial and dental developmental difficulties. There is no cure for Job’s syndrome, although antibiotics and antifungals are used to prevent and treat the infections associated with the disorder.

Steven M. Holland, M.D., chief of the NIAID Laboratory of Clinical Infectious Diseases, led the research team that over several years assembled the patient group that helped unravel the 41-year-old mystery. A key finding involved work with proteins that alert the body to increase production of white blood cells, increase immune-enhancing chemicals, and increase their killing of invaders. These signal transducer and activator of transcription (STAT) proteins help alert and direct immune system responses to stop invading pathogens. In 48 Job’s syndrome patients, Dr. Holland’s team sequenced the gene that makes STAT3 protein and discovered that mutations in the gene causes Job’s syndrome.

The team became interested in the role of the STAT3 gene after observing increased levels of some immune system responses in Job’s patients, but inadequate levels of response to others, indicating a defect in immune system signaling. Researchers found mutations in the STAT3 gene in 48 patients with Job’s, but not in 48 unaffected relatives or 158 unaffected people in a control group.

“We found that Job’s is associated with excessive immune reaction, not deficient immune reaction as many people suspected,” says Dr. Holland. “STAT3 is the key, and it can become a really powerful tool to dissect other aspects of immunity at a molecular and functional level.” For example, in studies done in mice, other investigators have demonstrated specific roles for STAT3 in bone and organ development, preservation and inflammation.

Ken Pekoc | EurekAlert!
Further information:
http://www.niaid.nih.gov
http://clinicalresearch.nih.gov/stories_schultz_m.html

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>