STAT3 Dominant-Negative Disease

STAT3 dominant-negative disease (STAT3DN)—also known as autosomal dominant hyper-IgE syndrome (AD-HIES) or Job’s Syndrome—results from mutations in the gene that encodes a signaling protein called STAT3. People with this disease tend to have very high levels of an antibody called immunoglobulin E (IgE), recurrent infections of the skin and lungs, recurrent bone fractures, unusually flexible joints, and inflamed skin.

Why Is the Study of STAT3 Dominant-Negative Disease a Priority for NIAID?

STAT3 dominant-negative disease has widespread deleterious effects on patients’ health, so NIAID scientists aim to develop and enhance treatments to improve patients’ quality of life. In addition, NIAID scientists hope that studying this disease will help them better understand the physiological processes associated with the genetic tendency to develop certain types of infections and allergic diseases.

How Is NIAID Addressing This Critical Topic?

NIAID investigators identified the role of STAT3 in this disease in 2007. Since then, NIAID-supported researchers have made multiple discoveries about how the loss-of-function mutation in the STAT3 gene leads to patients’ symptoms. NIAID-supported clinical research seeks to determine the effect of STAT3 dominant-negative disease on the immune system, including which immune cells and responses are affected and how these abnormalities translate into patients’ symptoms.