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Ataxia telangiectasia

Ataxia-telangiectasia (AT) (Boder-Sedgwick syndrome or Louis-Bar syndrome) is a primary immunodeficiency disorder that occurs in an estimated incidence of 1 in 40,000 to 1 in 300,000 births (Lederman, 2000). Telangiectasias are small, red 'spider' veins. These typically appear on the surface of the ears and cheeks or in the corners of the eyes in patients with AT. The 'ataxia' part of the name refers to the difficulty patients with AT have walking. At early age, the child's walking becomes wobbley, at teens handicapped-bound and at the early 20s, it becomes fatal. more...

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AT is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, progressive cerebellar dysfunction, and recurrent sinopulmonary infections secondary to progressive immunological and neurological dysfunction (Boder, 1958). AT patients are significantly predisposed to cancer, particularly lymphomas and leukemia. Other manifestations of the disease include sensitivity to ionizing radiation (Taylor et al., 1975), premature aging, and hypogonadism (Regueiro et al., 2000). AT has been a major interest of scientists since the 1960's because it may yield an insight into numerous other major health problems, such as cancer, neurological disease, immunodeficiency, and aging (Lederman, 2000).

The responsible gene in AT, ataxia-telangiectasia mutated (ATM), was discovered in 1995 by Savitsky et al., a team led by Yosef Shiloh of Tel Aviv University in Israel. Researchers linked the hyper-sensitivity of AT patients to ionizing radiation (IR) and predisposition to cancer to "chromosomal instability, abnormalities in genetic recombination, and defective signaling to programmed cell death and several cell cycle checkpoints activated by DNA damage"; (Canman, 1998). Earlier observations predicted that the gene altered in AT played a role in DNA damage recognition. These predictions were confirmed when a single gene on chromosome 11 (11q 22-23) was discovered (Savitsky et al., 1995, Gatti et al., 1982). Since its discovery, the protein product of the ATM gene has been shown to be a part of eukaryotic cell cycle control, DNA repair, and DNA recombination (Lavin, 2004).

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Immunoelectrophoresis
From Gale Encyclopedia of Medicine, 4/6/01 by Janis O. Flores

Definition

Immunoelectrophoresis, also called gamma globulin electrophoresis, or immunoglobulin electrophoresis, is a method of determining the blood levels of three major immunoglobulins: immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA).

Purpose

Immunoelectrophoresis aids in the diagnosis and evaluation of the therapeutic response in many disease states affecting the immune system. It is usually requested when a different type of electrophoresis, called a serum protein electrophoresis, has indicated a rise at the immunoglobulin level. Immunoelectrophoresis is also used frequently to diagnose multiple myeloma, a disease affecting the bone marrow.

Precautions

Drugs that may cause increased immunoglobulin levels include therapeutic gamma globulin, hydralazine, isoniazid, phenytoin (Dilantin), procainamide, oral contraceptives, methadone, steroids, and tetanus toxoid and antitoxin. The laboratory should be notified if the patient has received any vaccinations or immunizations in the six months before the test.

It should be noted that, because immunoelectrophoresis is not quantitative, it is being replaced by a procedure called immunofixation, which is more sensitive and easier to interpret.

Description

Immunoelectrophoresis is performed by placing serum on a slide containing a gel designed specifically for the test. An electric current is then passed through the gel, and immunoglobulins, which contain an electric charge, migrate through the gel according to the difference in their individual electric charges. Antiserum is placed alongside the slide to identify the specific type of immunoglobulin present. The results are used to identify different disease entities, and to aid in monitoring the course of the disease and the therapeutic response of the patient to such conditions as immune deficiencies, autoimmune disease, chronic infections, chronic viral infections, and intrauterine fetal infections.

There are five classes of antibodies: IgM, IgG, IgA, IgE, and IgD, but immunoelectrophoresis is ordered primarily to test for IgM, IgG, and IgA.

IgM is produced upon initial exposure to an antigen (for example, when a person receives the first tetanus vaccination, antitetanus antibodies of the IgM class are produced 10 to 14 days later). IgM is abundant in the blood but is not normally present in organs or tissues. IgM is primarily responsible for ABO blood grouping and rheumatoid factor, yet is involved in the immunologic reaction to other infections, such as hepatitis. Since IgM does not cross the placenta, an elevation of this immunoglobulin in the newborn indicates intrauterine infection such as rubella, cytomegalovirus (CMV) or a sexually transmitted disease (STD).

IgG is the most prevalent type of antibody, comprising approximately 75% of the serum immunoglobulins. IgG is produced upon subsequent exposure to an antigen. As an example, after receiving a second tetanus shot, or booster, a person produces IgG antibodies in five to seven days. IgG is present in both the blood and tissues, and is the only antibody to cross the placenta from the mother to the fetus. Maternal IgG protects the newborn for the first months of life, until the infant's immune system produces its own antibodies.

IgA constitutes approximately 15% of the immunoglobulins within the body. While it is found to some degree in the blood, it is present primarily in the secretions of the respiratory and gastrointestinal tract, in saliva, colostrum (the yellowish fluid produced by the breasts during late pregnancy and the first few days after childbirth), and in tears. IgA plays an important role in defending the body against invasion of germs through the mucous membrane-lined organs.

IgE is the antibody that causes acute allergic reactions; it is measured to detect allergic conditions. IgD, which constitutes the smallest portion of the immunoglobulins, is rarely evaluated or detected, and its function is not well understood.

Preparation

This test requires a blood sample. The patient should have nothing to eat or drink for 12 hours before the test.

Aftercare

Since this test is ordered when either very low or very high levels of immunoglobulins are suspected, the patient should be alert for any signs of infection after the test, including fever, chills, rash, or skin ulcers. Any bone pain or tenderness should also be immediately reported to the physician.

Risks

Risks for this test are minimal, but may include slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture, or bruising.

Normal results

Reference ranges vary from laboratory to laboratory and depend upon the method used. For adults, normal values are usually found within the following ranges:

  • IgM: 60-290 mg/dL
  • IgG: 700-1,800 mg/dL
  • IgA: 70-440 mg/dL.

Abnormal results

Increased IgM levels can indicate Waldenstrom's macroglobulinemia, a malignancy caused by secretion of IgM at high levels by malignant lymphoplasma cells. Increased IgM levels can also indicate chromic infections, such as hepatitis or mononucleosis; and autoimmune diseases, like rheumatoid arthritis.

Decreased IgM levels can be indicative of AIDS, immunosuppression caused by certain drugs like steroids or dextran, or leukemia.

Increased levels of IgG can indicate chronic liver disease, autoimmune diseases, hyperimmunization reactions, or certain chronic infections, such as tuberculosis or sarcoidosis.

Decreased levels of IgG can indicate Wiskott-Aldrich syndrome, a genetic deficiency caused by inadequate synthesis of IgG and other immunoglobulins. Decreased IgG can also be seen with AIDS and leukemia.

Increased levels of IgA can indicate chronic liver disease, chronic infections, or inflammatory bowel disease.

Decreased levels of IgA can be found in ataxia, a condition affecting balance and gait, limb or eye movements and/or speech; and telangiectasia, an increase in the size and number of the small blood vessels in an area of skin, causing redness. Decreased IgA levels are also seen in conditions of low blood protein (hypoproteinemia), and drug immunosuppression.

Key Terms

Antibody
A protein manufactured by the white blood cells to neutralize an antigen in the body. In some cases, excessive formation of antibodies leads to illness, allergy, or autoimmune disorders.
Antigen
A substance that can cause an immune response, resulting in production of an antibody, as part of the body's defense against infection and disease. Many antigens are foreign proteins not found naturally in the body, and include germs, toxins, and tissues from another person used in organ transplantation.
Autoimmune disorder
A condition in which antibodies are formed against the body's own tissues, for example, in some forms of arthritis.

Further Reading

For Your Information

    Books

  • Cahill, Mathew. Handbook of Diagnostic Tests. Springhouse, PA: Springhouse Corporation, 1995.
  • Jacobs, David S. Laboratory Test Handbook, Fourth Edition. Lexi-Comp Inc., 1996.
  • Pagana, Kathleen Deska. Mosby's Manual of Diagnostic and Laboratory Tests. St. Louis, MO: Mosby, Inc., 1998.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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