What is the definition of Autosomal Dominant Hyper IgE Syndrome?

Autosomal dominant hyper IgE syndrome (AD-HIES), formerly known as Job syndrome, affects several body systems including the immune system. AD-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood.  Signs and symptoms may include recurrent infections (e.g., pneumonia, skin infections), eczema, and occasionally bone and tooth abnormalities. The eczema and skin infections may cause rashes, blisters, collections of pus (abscesses), open sores, and scaling of the skin. Some cases of AD-HIES are caused by mutations in the STAT3 gene. In other cases, the cause is unknown.

What are the alternative names for Autosomal Dominant Hyper IgE Syndrome?

  • Hyper Ig E syndrome, autosomal dominant
  • HIES autosomal dominant
  • Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant
  • AD hyperimmunoglobulin E syndrome
  • Job syndrome autosomal dominant

What are the causes for Autosomal Dominant Hyper IgE Syndrome?

Most cases of AD-HIES are caused by mutations in the STAT3 gene . This gene provides instructions for making a protein that plays an important role in several body systems. The STAT3 protein is involved in controlling the activity of particular genes, including genes involved in the immune system, especially the T cells.

Changes in the STAT3 gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. The defective protein disrupts cellular functions such as immune system regulation. The resulting immune system abnormalities make people with AD-HIES highly susceptible to infections. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could explain why STAT3 gene mutations lead to the skeletal and dental abnormalities characteristic of AD-HIES. It remains unclear how STAT3 gene mutations lead to increased IgE levels. 

When AD-HIES syndrome is not caused by STAT3 gene mutations, the genetic cause of is unknown.

What are the symptoms for Autosomal Dominant Hyper IgE Syndrome?

Recurrent infections are common in people with autosomal dominant hyper IgE syndrome (AD-HIES). Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Recurrent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES). These skin problems cause rashes, blisters, collections of pus (abscesses), open sores, and scaling.

This condition also affects other parts of the body, including the bones and teeth. Many people with this condition have skeletal abnormalities such as an unusually large range of joint movement (hyperextensibility), an abnormal curvature of the spine (scoliosis), reduced bone density (osteopenia), and a tendency for bones to fracture easily. Dental abnormalities are also common in AD-HIES. The primary (baby) teeth do not fall out at the usual time during childhood, but are retained as the adult teeth grow in. Other signs and symptoms of AD-HIES can include distinctive facial features and structural abnormalities of the brain, which typically do not affect a person's intelligence.

Is Autosomal Dominant Hyper IgE Syndrome an inherited disorder?

Autosomal dominant hyper IgE syndrome (AD-HIES) has an autosomal dominant pattern of inheritance. This means that one copy of an altered gene in each cell is sufficient to cause the disorder. In about half of all cases, an affected person inherits a STAT3 mutation from an affected parent. Other cases result from new mutations in this gene. These cases occur in people with no history of the disorder in their family.

A small percentage (<5%) of individuals who have the clinical symptoms associated with AD-HIES do not have an identifiable mutation in the STAT3 gene. This suggests that there are additional unidentified mutations.

Clinical Trial
  • Status: Not yet recruiting
  • Phase: Early Phase 1
  • Intervention Type: Other
  • Participants: 70
  • Start Date: March 23, 2021
Skin Immunity Sample Collection Involving Blisters and Biopsies