« 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:

X-Linked Agammaglobulinemia (XLA)

Definition of XLA

XLA is an inherited form of PI disease in which people have a mutation in the gene needed for the development of B lymphocytes, the immune cells that produce antibodies (immunoglobulins).

X-Linked Agammaglobulinemia (XLA) symptoms X-Linked Agammaglobulinemia (XLA) symptoms

This mutation prevents the normal development of B lymphocytes, resulting in a severe deficiency in antibodies. Antibodies are an important part of the body's immune system and provide defense against infections.

The normal development of B cells into plasma cells which produce antibodies is a stepwise process that begins with cells called stem cells, which are found in the bone marrow.

Stem cells produce immature lymphocytes (white blood cells) called pro-B lymphocytes, which develop pre-B lymphocytes. These pre-B lymphocytes form B lymphocytes, or B cells. B lymphocyte cells mature into plasma cells that produce specific immunoglobulins when they come in contact with different disease-causing substances.

One of the first types of PI to be identified, XLA is sometimes called Bruton’s agammaglobulinemia, after the man who discovered it, or congenital agammaglobulinemia, due to a patient’s inability to produce antibodies.

The mutated gene responsible for the disease is located on the X chromosome. Since XLA is an X-linked disorder, only boys are affected; however, it had been known for several years that there were girls who had an immunodeficiency that looked just like XLA. The deficiency seen in girls is Autosomal Recessive Agammaglobulinemia (ARA). The genes responsible for ARA are not located on the X chromosome but result in a deficiency similar to XLA.

Symptoms of XLA

People with XLA develop frequent infections that involve the sinuses, ears, and lungs, but may also develop infections of the bloodstream and internal organs. In addition, gastrointestinal and skin infections can be a problem.

Physical examination of most patients with XLA reveals very small tonsils and lymph nodes (glands of the neck). This is because most of the bulk of the tonsils and lymph nodes is made up of B lymphocytes. In people with XLA the absence of B lymphocytes results in the reduced size of these tissues.

Diagnosis of XLA

Diagnosis of XLA or ARA should be considered in patients with recurrent or severe bacterial infections that also have small or absent tonsils and lymph nodes.

Screening for XLA begins with a blood test that looks for the presence of immunoglobulins, because all of the immunoglobulins (IgG, IgM, and IgA) are absent or exist only in small amounts in most people with XLA.

When a doctor suspects a person has XLA, an additional blood test will test for the percentage of B cells, the immune cells not produced in XLA. A low B cell count in the blood is the most reliable indicator of XLA or ARA.

Diagnosis can be confirmed by a test that establishes the absence of a protein called Bruton’s tyrosine kinase (BTK), which is associated with XLA, or by the detection of an abnormality in the BTK gene.

Treating X-Linked Agammaglobulinemia (XLA) Treating X-Linked Agammaglobulinemia (XLA)

Treating XLA

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.