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.
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 National Institute of Allergy and Infectious Diseases's (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 NIH team's report appears online in The New England Journal of Medicine. The Tokyo group published its findings in Nature last month.
Message posted by: Rashmi Nemade
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