Primary Immunodeficiency (PI) : Treatments, Part 4

by National Institute of Health

(Page 8 of 13)

IVIG isn't effective because there is no way to deliver IgA to mucous membranes. Moreover, some people with IgA Deficiency have anti-IgA antibodies, which can trigger a severe reaction to any blood products, including IVIG, that contain IgA.

The cause of IgA Deficiency is not known, and it may differ from one person to the next. B cells appear normal, but they seem unable to mature into cells capable of secreting IgA antibodies. Although no T cell defect has been found, some researchers suspect a problem with T cell regulation.

IgA Deficiency sometimes seems to run in families. It is more common among the relatives of people with CVID. In some cases, IgA Deficiency may progress to CVID.

IgA Deficiency itself seldom causes serious trouble. However, people with IgA Deficiency are very likely to have any of a variety of other problems. They are especially prone to allergies, including asthma; autoimmune diseases, including rheumatoid arthritis and diabetes; diseases of the gastrointestinal tract, and neurologic diseases. Thus anyone diagnosed with IgA Deficiency should have periodic checkups to look for such possibilities.

IgG Subclass Deficiency is another PI caused by the lack of certain antibodies. In this case, the person is missing one or two of the four subclasses of IgG (IgG1, IgG2, IgG3, and IgG4).

Each IgG subclass plays a slightly different role. IgG1 and IgG3 antibodies are formed in response to certain proteins, including toxins produced by some bacteria and the proteins of some viruses. IgG2 antibodies target the capsules that shield certain bacteria. Antibodies of some IgG subclasses cooperate with the complement system; others do not. As a result of such differences, each type of subclass deficiency leaves a person vulnerable to specific types of infections.

Overall IgG levels may be near normal, so it is necessary to measure each of the IgG subclasses. Patients may be immunized with a vaccine against encapsulated bacteria (such as Streptococcus pneumoniae or Haemophilus influenzae) to see if they respond with the appropriate antibodies.

Patients with IgG Subclass Deficiency have infections that are not as severe as those seen with broader immunoglobulin deficiencies such as XLA or CVID.

The usual treatment in IgG Subclass Deficiency consists of antibiotics to control and prevent infections. IVIG is usually reserved for children who are seriously ill and who are not responding to antibiotic therapy.

Combined T Cell and B Cell (Antibody) Deficiencies

Some cases of PI are the result of a combined deficiency. Both of the immune system's major weapons - antibodies and T cells - are disabled. In some, the deficiency is almost total, and nearly any infection is a threat to life. In many combined immunodeficiencies, the pattern of signs and symptoms creates a distinctive syndrome.

Severe Combined Immunodeficiency (SCID) is what most people think of when they hear about PI disease. It is the disease of "the boy in the bubble," who spent his life in an isolation chamber to protect himself from germs.

SCID is rare; chances of a child being born with SCID are about one in 500,000 births. Until recent years, it was always fatal.

There are several major causes of SCID. Each is caused by a different genetic defect, and each develops along a different pathway. In X-linked SCID, the most common type, a genetic flaw damages molecules that allow T cells and B cells to receive signals from crucial growth factors. Another type of SCID is ADA Deficiency. This condition results from the lack of an enzyme that helps cells - especially immune cells - get rid of toxic byproducts. Without ADA, poisons build up and kill the lymphocytes. Purine nucleoside phosphorylase (PNP) Deficiency results from a similar enzyme problem, but B cells are less affected and the immunodeficiency is less severe, although affected patients may have other problems (neurologic).

Yet another variation is known as MHC Class II Deficiency or Bare Lymphocyte Syndrome. MHC molecules are specialized proteins found on the surface of body cells and play an important role in bone marrow transplantation. Class II MHC molecules, which appear on many immune cells, allow B cells and other immune cells to recognize, interact with, and activate T cells. Without this B cell/T cell communication, the immune defenses are compromised.

Whatever the underlying problem that causes SCID, the consequences are nearly always the same. The child lacks almost all immune defenses, develops life-threatening infections, and needs major treatment to survive beyond infancy. Although the specifics vary from case to case, these children are vulnerable to serious infections caused by bacteria, as is typical with a B cell deficiency, and also by viruses and opportunistic germs, as is the case with a T cell deficiency.

Usually by the time a baby is three months old, he or she (because many cases of SCID are X-linked, SCID is more common in boys than in girls) is likely to have persistent thrush or extensive diaper rash. Weakened by chronic diarrhea, the baby may stop growing and gaining weight. Some children develop a sharp, persistent cough with Pneumocystis pneumonia, blood disorders, or chronic hepatitis. Meningitis and blood poisoning pose a constant threat.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.