Signs and Symptoms
People with STAT3 dominant-negative disease (STAT3DN) have very high levels of IgE and may have recurrent infections of the skin and lungs. These infections are often caused by the bacterium Staphylococcus aureus but also may be caused by other bacteria and fungi. Patients also tend to have recurrent bone fractures, unusually flexible joints, and inflamed skin, and may have a rash similar to eczema. Baby teeth in people with this disease often do not fall out on their own. People with STAT3DN also often have distinctive facial characteristics, such as uneven facial features, prominent forehead, deep-set eyes, broad nasal bridge, wide, fleshy nose tip, and protruding lower jaw.
In 2008, NIAID scientists discovered that important immune cells called Th17 cells are missing in people with STAT3DN. NIAID researchers also found in 2011 that an unusually low number of immune memory cells may cause people with the disease to be more susceptible to some viral infections. In 2013 and 2016, NIAID researchers showed that the STAT3 mutation protects people from more severe allergic disease by interfering with the process that causes typical allergic reactions.
A doctor will suspect STAT3DN in a person with eczema, very high IgE, recurrent boils, and pneumonias. Blood tests diagnosing the disease will show normal levels of IgG, IgA, and IgM antibodies but very high levels of IgE antibodies. People with the disease also may show a high number of white blood cells called eosinophils and a poor response to immunizations. Sequencing of the patient’s DNA can confirm the presence of the STAT3 mutation.