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Immunoglobulin Deficiency Syndromes

Overview :

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

  • 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 secretions.
  • IgD activity is not well understood.
  • IgE is present in the respiratory secretions. It is an antibody for parasitic diseases, Hodgkin's disease, hay fever, atopic dermatitis, and allergic asthma.

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.

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 intestines.
  • 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 is not 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 IgG antibodies. This disease is the result of a genetic mutation.

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