« Understanding Primary Immunodeficiency (PI)

Types of PI

Primary immunodeficiency (PI) diseases are characterized in many different ways, including:

  • Low antibody levels
  • Defects in antibodies
  • Defects in the cells and proteins of the immune system (for example, T cells, B cells, neutrophils, or the complement system)

These defects make people susceptible to recurrent infections, and other complications that may require different therapies. The most common primary immunodeficiency types result in an inability to make a very important type of protein called antibodies or immunoglobulins, which help the body fight off infections from bacteria or viruses. In addition to increased susceptibility to infection, people with PI may also have autoimmune diseases in which the immune system attacks their own cells or tissues.

PI Type:

Hyper-IgM (HIGM) Syndrome

Definition of HIGM Syndrome

Hyper-IgM Syndrome Hyper-IgM Syndrome

As the name suggests, people with hyper-IgM (HIGM) syndrome have an excess of IgM and reduced levels of other immunoglobulins, including IgG and IgA. This happens because the body cannot change production of IgM to other antibodies. While the body's B lymphocytes, or B cells, can produce IgM on their own, they require assistance from T lymphocytes (or T cells) to switch production from IgM to IgG, IgA or IgE.

There are a number of genetic defects that result in HIGM syndrome:

  • The most common form of HIGM syndrome results from a defect or deficiency of a protein on the surface of T cells that makes them unable to instruct B cells to switch from making IgM to making other immunoglobulins. Called X-linked HIGM (XHIGM) syndrome, this form of HIGM syndrome is passed along as an X-linked recessive trait and is usually found only in boys.
  • Other forms of HIGM syndrome are inherited by both boys and girls as autosomal recessive traits. Since the autosomal recessive forms of HIGM require that the gene on both chromosomes be affected, they are less frequent than the X-linked conditions.
  • The last type of HIGM syndrome is associated with a skin condition called ectodermal dysplasia, where patients have sparse hair and conical teeth, and recurrent infections. This is another X-linked trait that affects a molecule needed to signal switching of immunoglobulin production.

Symptoms of HIGM Syndrome

HIGM Syndrome diagnosis HIGM Syndrome diagnosis

Most children with HIGM syndrome will develop symptoms within the first or second year of life. The most common problem is an increased risk of infection, including repeated upper and lower respiratory tract infections. Most infections are bacterial, but they can also be viral or fungal. Some patients also experience gastrointestinal issues including diarrhea and difficulty absorbing nutrients from food (malabsorption).

Patients with XHIGM syndrome may develop an opportunistic form of pneumonia, or a gastrointestinal infection that can cause severe liver disease. About half of patients with XHIGM develop a low white blood cell count (neutropenia), which is associated with mouth ulcers, inflammation or ulceration of the rectum, and skin infections.

Patients with autosomal recessive HIGM are more likely to experience enlargement of the lymph nodes and the spleen. As a result, these people often have enlarged tonsils and adenoids that may cause snoring and obstructive sleep apnea. Autoimmune diseases, where a person's immune system attacks the body, may also occur in patients with HIGM.

Diagnosis of HIGM Syndrome

HIGM syndrome is suspected in a patient presenting with severe recurrent respiratory infections or an opportunistic infection when blood tests show a normal or elevated level of IgM and low or absent IgG. Final diagnosis is based on an analysis of the person's DNA to identify mutations in genes known to cause HIGM syndrome.

Treating HIGM Syndrome

Only your doctor can determine which treatment is right for you and your specific health needs. Visit our Treating PI section to read about the types of PI treatment and download questions to ask your doctor.