Immunoglobulin Deficiency Syn... Health Article

Demographics

Primary immunoglobulin deficiency syndromes occur only rarely. Those that are X-linked occur more in males than females; other immunoglobulin deficiencies occur equally in both sexes. Detection of the syndromes usually occurs in childhood. Numbers of new cases of specific syndromes are difficult to estimate because many deficiencies go undiagnosed. Among the syndromes for which incidence rates are available are IgA deficiency (one in 500–700), agammaglobulinemia (one in 50,000–100,000), severe combined immunodeficiency or SCID (one in 100,000–500,000), and common variable immunodeficiency or CVID (one in 50,000–200,000).

Causes and symptoms

Primary immunoglobulin deficiencies are primarily the result of congenital defects that affect the development and function of B lymphocytes (B cells), the white cells that fight infection and disease. Defects can occur at two main points in the development of B-cells. First, B cells can fail to develop into antibody-producing cells. X-linked agammaglobulinemia is an example of this disease. Secondly, B cells can fail to make a particular type of antibody or fail to switch classes during maturation. Initially, when B cells start making antibodies for the first time, they make IgM. As they mature and develop memory, they switch to one of the other immunoglobulin classes. Failure to switch or failure to make a subclass can lead to immunoglobulin deficiency diseases. Defects in the thymus gland that manufactures T lymphocytes or defects in the T lymphocytes themselves can also result in reduced production of immunoglobulins.

Symptoms are frequent and so are persistent infections, particularly of the respiratory system. Frequent digestive disturbances and diarrhea may lead to malab-sorption of essential nutrients and failure to thrive. Children with primary immunoglobulin deficiency syndromes will exhibit some of the following characteristics:

• signs of infection in the first days or weeks of life
• a slow response to treatment
• infection suppressed by appropriate treatment but not cured
• common bacterial or viral organisms causing increasingly acute recurring infections
• uncommon bacterial or viral organisms causing infection
• multiple simultaneous infections at more than one site
• delays in growth and development
• development of unexpected complications such as anemias and chronic diseases

When to call the doctor

Parents should seek medical care from a pediatrician or family practitioner if their young child or teenager has frequent or persistent infections such as upper respiratory infections, or chronic cough, ear infections, sinusitis, asthma, or pneumonia. Sores that do not heal or recurring or long-lasting skin irritations may also be signs of reduced immune system functioning.

Diagnosis

An immunodeficiency disease is suspected when children become ill frequently, especially repeat illness caused by the same organisms. Diagnosis will begin with a detailed history of the child's illnesses (dates, duration, and infection site) and review of all prior medications and immunizations and results of diagnostic tests performed. Determining which immunoglobulins are present and which are absent or present in reduced amounts is critical for diagnosis. Diagnostic testing may include routine blood tests such as a complete blood count (CBC) and differential (peripheral blood smear) to evaluate overall health and determine the type and number of red cells, white cells, and platelets present in the blood. Tests or cultures may be performed to determine the type of bacteria or virus causing recurring infections. B lymphocytes and T lymphocytes may be quantified. When immunodeficiency is suspected, levels of the classes of immunoglobulins are measured in blood serum by using a clinical laboratory procedure called electrophoresis. This procedure both quantifies the amount of each antibody present and identifies the various classes and subclasses of antibodies. Deficiencies may be noted in one class or subclass or in combinations of antibodies. Genetic testing may be done to help identify the type of immunodeficiency disease.

Treatment

Immunoglobulin deficiency diseases cannot be cured, but treatment that replaces or boosts specific immunoglobulins can help support immune function in affected children. Immune serum, obtained from donated blood that contains adequate levels of IgG antibodies, may sometimes be transfused as a source of antibodies to boost the immune response, even though it may not contain all antibodies needed and may lack antibodies specific for some of the recurring infections. The preferred treatment is to give specific immunoglobulins intravenously (immunoglobulin intravenous therapy or IVIG) or subcutaneously. No replacement therapy is available for treating IgA deficiencies.

Treatment will also focus on controlling infections in immunodeficient children. Immunization against frequent infection can be achieved in some children by administering polysaccaride-protein conjugate vaccines shown to improve immune response in certain types of infection. Antibiotics are used routinely at the first sign of an infection to help eliminate infectious organisms. Antifungal drug therapy may be administered to treat fungus infections. Few drugs are effective against viral diseases, and each viral illness will be evaluated and treated differently, depending on the virus and the overall health of the child. Bone marrow transplantation may correct immunodefiency in some cases.