Autosomal Dominant Hyper-IgE Syndrome (Job Syndrome)

Autosomal Dominant Hyper-IgE Syndrome (Job Syndrome) is a rare genetic disorder that mainly affects the immune system. People with this condition have very high levels of a type of antibody called IgE, which normally helps fight infections. The syndrome causes frequent and severe skin infections, lung infections, and other problems with the immune system. It also leads to distinctive physical features like a broad nose and joint flexibility. Because the immune system does not work properly, affected individuals are more prone to infections caused by bacteria and fungi. The condition impacts overall health by making it harder for the body to fight off infections and heal wounds.

Autosomal Dominant Hyper-IgE Syndrome (Job Syndrome) is a primary immunodeficiency characterized by markedly elevated serum IgE levels, recurrent staphylococcal skin abscesses, and pneumonias often complicated by pneumatoceles. It is caused by dominant-negative mutations in the STAT3 gene, leading to defective Th17 cell differentiation and impaired neutrophil recruitment. This results in susceptibility to recurrent bacterial and fungal infections, especially by Staphylococcus aureus and Candida species. Patients also exhibit characteristic connective tissue abnormalities such as hyperextensible joints, scoliosis, and distinctive facial features. The syndrome is clinically significant due to its chronic infectious complications and potential for severe lung damage.