Scientists have made another major breakthrough--the second in the past year--in understanding a rare immune disorder called Job's syndrome.
Job's syndrome is characterized by recurrent and often severe bacterial and fungal infections leading to outbreaks of abscesses and boils. Other symptoms of the disease include lung infections, problems in facial and dental development, curved spine and high risk of bone fractures. While individuals with Job's syndrome often have normal life spans with intensive medical supervision, life-threatening complications from infections are a constant concern.
Now, scientists at the National Institutes of Health (NIH) have shown that Job's sufferers lack a specific type of infection-fighting white blood cell called Th17 cell, making them vulnerable to attacks by bacteria and fungi. The study was a collaborative effort of investigators from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), both components of NIH.
Th17 cells produce a protein called interleukin-17 (IL-17) and are known to play a major role in protection against invading pathogens. They are critical for recruiting other microbe-fighting immune cells called neutrophils to the site of infection. The study, which included 13 patients diagnosed with Job's syndrome, revealed that Th17 cells were lacking in these patients. This is also the first demonstration of a human genetic disease where researchers have not been able to generate Th17 cells in laboratory experiments using blood samples from patients with Job's syndrome.
The new findings strongly suggests that Th17 cells are important in the control of Staphylococcus bacteria and certain fungal infections and the research has the potential to uncover why certain people who do not have Job's syndrome are prone to Staphylococcus and other fungal infections.
Although only 250 cases of Job's syndrome have been reported since the disease was first described in 1966, NIH scientists have been studying the disease for 30 years. In September 2007, NIAID issued a press release about the first major breakthrough. NIAID scientists and their colleagues had discovered a mutation in the gene that makes a specific protein known to help alert and direct immune system responses to stop invading pathogens. The proteins coded by this gene are called signal transducer and activator of transcription 3 (STAT3).