Immunoglobulin Deficiency Syn... Health Article

Definition

Immunoglobulin deficiency syndromes are a group of disorders that involve defects of any component of the immune system or a defect of another system that affects the immune system, leading to an increased incidence or severity of infection. In these disorders, specific diseasefighting antibodies (immunoglobulins such as IgG, IgA, and IgM) are either missing or are present in reduced levels. Children who have immunodeficiency syndromes may be subject to infection, diseases, disorders, or allergic reactions to a greater extent than individuals with fully functioning immune systems.

Description

Immunodeficiency is a defect of any component of the immune system or a defect of another system that affects the immune system leading to an increased incidence or severity of infection. Immunoglobulin deficiencies refer to missing or reduced levels of immunoglobulin (IgG, IgA, IgM) associated with an inability to make adequate specific antibody. These antibodies are specific proteins (immunoglobulins) produced by the immune system to respond to bacteria, viruses, fungi, parasites, or toxins that invade the body. Each class of antibody binds to corresponding molecules (antigens) on the cell surfaces of certain foreign organisms or substances, attempting to protect the body against reactions or illness. When the immune system is challenged by invading organisms, the antibodies may each play a protective role:

• Immunoglobulin G (IgG) is the most abundant class of immunoglobulins, directed toward viruses, bacterial organisms, and toxins. It is found in most tissues and in plasma, the clear portion of blood.
• Immunoglobulin M (IgM) is the first antibody produced in an immune response to any invading organism or toxic substance.
• Immunoglobulin A (IgA) is activated early in response to invasion by bacteria and viruses. It is found in saliva, tears, and all other mucus secretions.
• As of the early 2000s, IgD activity is not well understood.
• Immunoglobulin E (IgE) is found in respiratory secretions and is directed toward invasion of the body by parasites and in allergic reactions such as hay fever, atopic dermatitis, and allergic asthma.

Immunoglobulins are made by white blood cells known as B cells (B lymphocytes). Any disease that harms the development or function of B cells will, therefore, affect the production of immunoglobulin antibodies. T cells, another type of white blood cell, may also be involved in immunodeficiency disorders. About 70 percent of immunoglobulin deficiencies involve B lymphocytes and 20–30 percent involve T lymphocytes. Another 10 percent may involve both B and T lymphocytes.

Many of the infections that occur in children with immunoglobulin deficiency syndromes are caused by bacterial organisms or microbes. Certain of these invasive organisms form capsules when they enter the body, a mechanism used to confuse the immune system. In a healthy body with an adequately functioning immune system, immunoglobulin antibodies bind to the capsule and overcome the bacteria's defenses. Streptococci, meningococci, and Haemophilus influenzae, organisms that cause diseases such as otitis media, sinusitis, pneumonia, meningitis, osteomyelitis, septic arthritis, and sepsis, all make capsules. Children with immunoglobulin deficiencies are also prone to viral infections, including echovirus, enterovirus, and hepatitis B. They may also develop infection after receiving live (attenuated) polio vaccine. This is one of the reasons that live polio vaccine is no longer used routinely in the United States.

There are two types of immunodeficiency diseases: primary and secondary. Immunoglobulin deficiency syndromes are primary immunodeficiency diseases. They account for 50 percent of all primary immunodeficiencies and are the largest group of immunodeficiency disorders. Some are well defined and some are not fully understood. Secondary disorders occur in normally healthy people who are suffering from an underlying disease that weakens the immune system. Successful treatment of the disease usually reverses the immunodeficiency.

Examples of well defined immunoglobulin deficiency disorders include the following:

• X-linked agammaglobulinemia is an inherited disease stemming from a defect on the X chromosome, consequently affecting more males than females. Defect results in absence or reduced numbers of B cells that do not mature and perform normal function. 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 immunoglobulin antibodies are decreased in agammaglobulinemia.
• Immunoglobulin heavy chain deletion, a form of agammaglobulinemia, is a genetic disorder in which part of the antibody molecule is absent. This condition 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.
• X-linked hypogammaglobulinemia can occur in combination with growth hormone (GH) deficiency, producing short stature and delayed puberty, primarily in boys but also occurring in girls.
• 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, children may have decreased levels of IgG and IgA antibodies. In some infants with this disorder, laboratory tests are able to show that the antibodies present do not react properly with infectious bacteria.
• IgG subclass deficiency is a disorder associated with a poor ability to respond and make antibody against polysaccharide antigens, primarily pneumococcus.
• Selective IgA deficiency is an inherited disease characterized by a failure of B cells to switch from making IgM to IgA antibodies. The amount of IgA produced is limited in either serum or the mucosal linings of organs. This condition may result in more infections of mucosal surfaces, such as the nose, throat, lungs, and intestines. However, most persons with this abnormality are asymptomatic.
• IgM deficiency is characterized by the absence or low level of total IgM antibodies, the body's first defense against infection. This condition results in slow response to infective organisms and slow response to treatment.
• IgG deficiency with hyper-IgM is a disorder that results when B-cells fail to switch from making IgM to IgG. This condition produces an increase in the amount of IgM antibodies present and a decrease in the amount of IgG and IgA antibodies. This disorder is the result of a genetic mutation.
• Severe combined immunodeficiency (SVID) is not precisely an immunoglobulin deficiency, but a combined deficiency resulting from a T-cell disorder. The T-cell dysfunction can either be X-linked, affecting more males than females and characterized by the absence of T lymphocytes, or it can occur through autosomal inheritance (not sex linked), resulting in an absence of both T and B lymphocytes and a deficient thymus gland, the lymphoid organ that produces T-cell lymphocytes.
• Common variable immunodeficiency (CVID) is a primary immunodeficiency with onset of symptoms typically occurring in the second or third decade of life. It is never diagnosed before two years of age and is diagnosed only after drug toxicity and other primary immune deficiencies have been ruled out. IgG and IgA and/or IgM will be measured at about two standard deviations below normal. The individual will typically not make antibodies against protein or polysaccharide antigens and will not make IgM antibodies against incompatible blood group antigens (hemagluttinins). T-cell dysfunction is the variable in this disorder. Children who have this disorder are subject to recurring infections and may not respond appropriately to immunization.