X-linked severe combined immunodeficiency

Definition

Immunoglobulin deficiency syndromes are a group of immunodeficiency disorders in which the patient has reduced number of or lack of antibodies.

Description

Immunoglobulins (Ig) are antibodies. There are five major classes of antibodies: IgG, IgM, IgA, IgD, and IgE.

All antibodies are made by B-lymphocytes (B-cells). Any disease that harms the development or function of B-cells will cause a decrease in the amount of antibodies produced. Since antibodies are essential in fighting infectious diseases, people with immunoglobulin deficiency syndromes become ill more often. However, the cellular immune system is still functional, so these patients are more prone to infection caused by organisms usually controlled by antibodies. Most of these invading germs (microbes) make capsules, a mechanism used to confuse the immune system. In a healthy body, antibodies can bind to the capsule and overcome the bacteria's defenses. The bacteria that make capsules include the streptococci, meningococci, and Haemophilus influenzae. These organisms cause such diseases as otitis, sinusitis, pneumonia, meningitis, osteomyelitis, septic arthritis, and sepsis. Patients with immunoglobulin deficiencies are also prone to some viral infections, including echovirus, enterovirus, and hepatitis B. They may also have a bad reaction to the attenuated version of the polio virus vaccine.

• IgG is the most abundant of the classes of immunoglobulins. It is the antibody for viruses, bacteria, and antitoxins. It is found in most tissues and plasma.
• IgM is the first antibody present in an immune response.
• IgA is an early antibody for bacteria and viruses. It is found in saliva, tears, and all other mucous secreations.
• IgD activity is unknown.
• IgE is present in the respiratory secretions. It is an antibody for parasitic diseases, Hodgkin's disease, hay fever, atopic dermatitis, and allergic asthma).

There are two types of immunodeficiency diseases: primary and secondary. Secondary disorders occur in normally healthy bodies that are suffering from an underlying disease. Once the disease is treated, the immunodeficiency is reversed. Immunoglobulin deficiency syndromes are primary immunodeficiency diseases, occurring because of defective B-cells or antibodies. They account for 50% of all primary immunodeficiencies, and they are, therefore, the most prevalent type of immunodeficiency disorders.

• X-linked agammaglobulinemia is an inherited disease. The defect is on the X chromosome and, consequently, this disease is seen more frequently in males than females. The defect results in a failure of B-cells to mature. Mature B-cells are capable of making antibodies and developing "memory," a feature in which the B-cell will rapidly recognize and respond to an infectious agent the next time it is encountered. All classes of antibodies are decreased in agammaglobulinemia.
• Selective IgA deficiency is an inherited disease, resulting from a failure of B-cells to switch from making IgM, the early antibody, to IgA. Although the B-cell numbers are normal, and the B-cells are otherwise normal (they can still make all other classes of antibodies), the amount of IgA produced is limited. This results in more infections of mucosal surfaces, such as the nose, throat, lungs, and intestine.
• Transient hypogammaglobulinemia of infancy is a temporary disease of unknown cause. It is believed to be caused by a defect in the development of T-helper cells (cells that recognize foreign antigens and activate T- and B-cells in an immune response). As the child ages, the number and condition of T-helper cells improves and this situation corrects itself. Hypogammaglobulinemia is characterized by low levels of gammaglobulin (antibodies) in the blood. During the disease period, patients have decreased levels of IgG and IgA antibodies. In lab tests, the antibodies that are present do not react well with infectious bacteria.
• Common variable immunodeficiency is a defect in both B cells and T-lymphocytes. It results in a near complete lack of antibodies in the blood.
• Ig heavy chain deletions is a genetic disease in which part of the antibody molecule isn't produced. It results in the loss of several antibody classes and subclasses including most IgG antibodies and all IgA and IgE antibodies. The disease occurs because part of the gene for the heavy chain has been lost.
• Selective IgG subclass deficiencies is a group of genetic diseases in which some of the subclasses of IgG are not made. There are four subclasses in the IgG class of antibodies. As the B-cell matures, it can switch from one subclass to another. In these diseases there is a defect in the maturation of the B-cells that results in a lack of switching.
• IgG deficiency with hyper-IgM is a disease that results when the B-cell fails to switch from making IgM to IgG. This produces an increase in the amount of IgM antibodies present and a decrease in the amount of IgGaantibodies. This disease is the result of a genetic mutation.

Causes & symptoms

Immunoglobulin deficiencies are the result of congenital defects affecting the development and function of B lymphocytes (B-cells). There are two main points in the development of B-cells when defects can occur. First, B-cells can fail to develop into antibody-producing cells. X-linked agammablobulinemia 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 four classes of antibodies. Failures in switching or failure to make a subclass of antibody leads to immunoglobulin deficiency diseases. Another mechanism which results in decreased antibody production is a defect in T-helper cells. Generally, defects in T-helper cells are listed as severe combined immunodeficiencies.

Symptoms are persistent and frequent infections, diarrhea, failure to thrive, and malabsorption (of nutrients).

Diagnosis

An immunodeficiency disease is suspected when children become ill frequently, especially from the same organisms. The profile of organisms that cause infection in patients with immunoglobulin deficiency syndrome is unique and is preliminary evidence for this disease. Laboratory tests are performed to verify the diagnosis. Antibodies can be found in the blood. Blood is collected and analyzed for the content and types of antibodies present. Depending on the type of immunoglobulin deficiency the laboratory tests will show a decrease or absence of antibodies or specific antibody subclasses.

Treatment

Immunodeficiency diseases can not be cured. Patients are treated with antibiotics and immune serum. Immune serum is a source of antibodies. Antibiotics are useful for fighting bacteria infections. There are some drugs that are effective against fungi, but very few drugs that are effective against viral diseases.

Bone marrow transplantation can, in most cases, completely correct the immunodefiency.

Prognosis

Patients with immunoglobulin defiency syndromes must practice impecable health maintenance and care, paying particular attention to optimal dental care, in order to stay in good health.

Key Terms

Antibody

Another term for immunoglobulin. A protein molecule that specifically recognizes and attaches to infectious agents.

T-helper cell

A type of cell that recognizes foreign antigens and activates T- and B-cells in an immune response.

Further Reading

For Your Information

Books

• Abbas , A.K., A.H. Lichtman, and J.S. Pober. Cellular and Molecular Immunology. Philadelphia: W.B. Saunders Company, 1997.
• Berkow, Robert, ed. Merck Manual of Medical Information. Whitehouse Station, NJ: Merck Research Laboratories, 1997.
• Roit, I.M. Roitt's Essential Immunolgy. Oxford: Blackwell Science Ltd., 1997.

Gale Encyclopedia of Medicine. Gale Research, 1999.