« 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:

IgG Subclass Deficiency

Definition of IgG Subclass Deficiency

IgG Subclass Deficiency IgG Subclass Deficiency

There are five classes of antibodies (immunoglobulins) that help the body fight infection: IgG, IgA, IgM, IgD, and IgE. Immunoglobulins make up the antibodies that fight infection. Most of the antibodies in the blood and other fluids that surround the body’s tissues and cells are of the IgG class. IgG is divided into four subclasses: IgG1, IgG2, IgG3, and IgG4. People are said to have an IgG subclass deficiency when they lack or have very low levels of one or two IgG subclasses, but have normal levels of other immunoglobulins.

Each IgG subclass plays a slightly different role in protecting the body against infection. Therefore, a person lacking a specific IgG subclass will be vulnerable to certain kinds of infections but not others. For example, the IgG1 and IgG3 subclasses contain antibodies against serious bacterial infections such as diphtheria and tetanus, as well as antibodies against viral proteins. In contrast, the IgG2 subclass contains antibodies against the polysaccharide coating of certain disease-producing bacteria that can cause ear and sinus infections, pneumonia, blood infections and meningitis.

The IgG circulating in the bloodstream is 60%-70% IgG1, 20%-30% IgG2, 5%-8% IgG3, and 1%-3% IgG4. With age, the amount of the different IgG subclasses circulating will change. In children especially, this factor must be considered when determining whether a subclass level is abnormal, either in terms of having a low IgG subclass level or the inability to make a specific antibody.

Conditions of IgG Subclass Deficiency

Recurring ear and sinus infections, sinusitis, bronchitis, and pneumonia are the most frequent illnesses in people with IgG subclass deficiencies. Some people have an increased frequency of infections by an early age; others will not experience infections until later.

IgG Subclass Deficiency diagnosis IgG Subclass Deficiency diagnosis

Diagnosis involves measurement of IgG subclassess in addition to assessment of total IgG.

Diagnosis of IgG Subclass Deficiency

A person is considered to have a selective IgG subclass deficiency if blood levels of one or more of the IgG subclasses are below the normal range based on age, and the levels of other immunoglobulins (total IgG, IgA, and IgM) are normal or near normal.

As a person may have no or very low levels of one or more IgG subclasses while maintaining a normal level of total IgG, diagnosis requires measurement of IgG subclasses in addition to serum IgG, IgA, and IgM. IgG4 deficiency often occurs in combination with IgG2 deficiency.

It’s important to remember that the definition of “normal” IgG subclass concentrations varies over time, and from lab to lab. Normal values usually represent a small range below and above the average for a person’s age.

An additional subset of patients have normal levels of immunoglobulin and normal IgG subclasses, yet fail to develop protective antibody levels in response to infections with Streptococcus pneumoniae or vaccines against the bacteria. These people are thought to have a specific antibody deficiency and are usually grouped with patients with IgG subclass deficiency.

Treating IgG Subclass Deficiency

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.