Job syndrome, first described in 1966, is a rare immunodeficiency disorder affecting one in a million people. It is characterized by the presence of high levels of an antibody called immunoglobulin (IgE) in the blood. Patients are greatly susceptible to fungal and bacterial infections as their immune systems become highly sensitive to microbes.
Job Syndrome, also known as Hyperimmunoglobulin E Syndrome is an immunodeficiency disorder and is characterized by high levels of the antibody immunoglobulin (IgE) in the blood. Usually, IgE is triggered as a response to parasitic worms or other invaders, and people with Job syndrome have an abnormal response, thereby producing high levels of IgE in the blood. The reason though is still unknown. This syndrome was described first in 1966, and since then only around 250 cases, have been reported worldwide. This is a rare condition and occurs in one in a million, however, it will never be known how many non-reported cases were there or exist.
This syndrome gets its name from the Biblical character, Job. He was a person who was afflicted by skin sores and skin abscesses, in the course of a faith test from God. Since this syndrome features recurrent skin abscesses, it was titled Job syndrome. This syndrome causes the immune system to become highly sensitive (puts the immune system out of job) to invading microbes (fungal and bacterial infections). Thus, people suffering from this condition are seen to be affected by skin lesions, boils, abscesses and so on. Besides skin abscesses, this condition is also characterized by pneumonia with pneumatocele development, and high serum levels of IgE. There are high risks of developing a curved spine, facial and dental deformities and bone breakage.
The causes of Job syndrome has been oblivious to us, since the time it was first described 33 years ago. However, scientists have made certain remarkable discoveries in 2007 and 2008. In 2007, a study conducted by scientists at National Institutes of Health (NIH) found that mutations caused in STAT3 gene was one of the reasons why Job syndrome occurred. STAT3 gene provides STAT3 protein with instructions regarding its functioning such as cell division, cell movement, cell growth and self destruction of cells (apoptosis). In order to carry out these functions, the protein gets itself attached to the DNA and further controls the activities of other genes.
Mutations in STAT3 gene alters the functioning of STAT3 protein, thereby impairing its ability to control the activity of other genes. The erroneous gene destroys the immune system regulation, which is why these patients are highly susceptible to bacterial and fungal infections. Since STAT3 is also responsible for cell growth which happens in the bone tissues, its mutation affects the skeletal system as well. An autosomal dominant pattern of inheritance is commonly seen in Job syndrome, which means that even if one copy of mutated gene is present in the cell, it is enough to cause this disorder.
Almost half of the cases are the ones who have inherited the altered gene from their parents. In some people, mutation is caused freshly in their body and have no Job syndrome history in their family. However, not every Job syndrome case is caused due to STAT3 gene mutation. In 2008, scientists at (NIH) stated that Job syndrome patients lack Th17 cells, which are a specific type of infection-fighting white blood cells, which is why the body becomes so susceptible to attacks from bacteria and fungi. The institute conducted a study on 13 patients and found that Th17 cells were lacking in their blood.
Th17 cells play vital role in controlling fungal and bacterial infections, as they produce a protein called interleukin-17 (IL-17). This protein plays a major role in protecting the body against foreign bodies, bacteria and viruses. They are responsible for recruiting neutrophils (microbe-fighting immune cells) to the infection site. Scientists and researchers are still trying to find the relationship between Th17 and high levels of IgE in the blood. They are conducting studies that will show them a relationship between the two, and that in the absence of Th17, the IgE level rises.
Job syndrome does not affect people of a particular gender, age, location or race. Various antibiotics and antifungals are used to treat the infections that arise, although, as of now no cure for this syndrome exists. It results in gradual death of the individual. With intensive medical supervision, these sufferers can have normal life spans, however, life-threatening complications from infections remain a constant concern.
