Lymphocyte immune globulin

Definition

Lymphocyte immune globulin is a drug used to suppress the immune system. Lymphocyte immune globulin is also known by the generic name anti-thymocyte globulin (ATG) and the brand names Atgam and Thymoglobulin. Atgam first received FDA approval in 1981 and Thymoglobulin in 1999. As of 2001, no generic preparations are available.

Purpose

Lymphocyte immune globulin is used to treat aplastic anemia and to prevent rejections during bone marrow transplantation . This drug has also been used experimentally to treat advanced non-Hodgkin's lymphomas and cutaneous T-cell lymphoma .

Description

This drug suppresses the immune system by slowing down T cells, cells critical in immunity. Without them, the immune system is essentially paralyzed. Lymphocyte immune globulin contains antibodies that attach to T cells and prevent them from working properly. This drug also decreases the number of T cells in the blood.

Lymphocyte immune globulin is made by vaccinating an animal with immature human T cells, then collecting the antibodies made against them. Atgam is made in horses and Thymoglobulin in rabbits.

Atgam is labeled for use only in kidney transplantation and aplastic anemia, and Thymoglobulin is specifically approved only for kidney transplantation. The effectiveness of either drug for treating aplastic anemia in cancer patients, however, is unknown.

Lymphocyte immune globulin is often used off-label to treat graft-versus-host disease (GVHD) after bone marrow transplantation. The drug has been beneficial for GVHD patients in some studies, but its effectiveness has not been conclusively demonstrated. In some clinical trials , it is also being used to prepare the patient's body for bone marrow transplantation. This drug produces short partial remissions of some lymphomas in published experiments.

Recommended dosage

The usual dose of Atgam in adults is 10-30 mg/kg (1 kilogram is 2.2 pounds). Doses of 5-25 mg/kg have been given to a few children. Thymoglobulin, which is about 10 times stronger, has a recommended dose of 1-1.5 mg/kg in adults. Typically these drugs are given daily or every other day for several days or weeks. They are injected into the blood over several hours, under close supervision in the hospital or clinic.

Precautions

Patients should not take Atgam if they are allergic to horse proteins or Thymoglobulin if they are allergic to rabbit proteins. Patients should tell their doctor about any current or previous blood cell problems and about all their prescription and over-the-counter drugs.

Lymphocyte immune globulin can make infections more serious. Patients should check with their doctor if they have any symptoms of an infection, such as chills, fever , or sore throat. They should also avoid people with contagious diseases and anyone recently vaccinated with an oral polio vaccine. The drug decreases the effectiveness of vaccinations given just before or during treatment. Some types of vaccines are not safe to receive while taking this drug.

Lymphocyte immune globulin does not interact with any specific foods. However, patients should check with their doctor for specific recommendations for eating and drinking before the treatment.

Patients should be careful in planning their activities, as this drug can cause dizziness.

Side effects

Thymoglobulin and Atgam have very similar side effects. However, Thymoglobulin is approximately twice as likely to decrease the number of white blood cells and three times as likely to result in malaise. Dizziness is much more common with Atgam. Other numerous side effects caused by both drugs include:

• Chills or fever in most patients
• Risk of developing an infection, which has been seen in up to 30% of patients, and sepsis in approximately 10%
• Risk of bleeding, due to thrombocytopenia (seen in 30-45% of patients)
• Rarely, anemia or the destruction of white blood cells other than T cells
• Pain, swelling, and redness where the drug is injected (minimized by injecting the drug into the faster-moving blood in a large vein)
• Allergic reactions (Serious allergic reactions can cause difficulty breathing, swelling of the tongue, a drop in blood pressure, or pain in the chest, sides, or back. Severe allergic reactions are potentially life-threatening, but rare; milder allergic reactions can result in itching , hives, or rash. Skin tests are often done to predict the likelihood of an allergic reaction, but are not foolproof.)
• Serum sickness, an immune reaction against the drug (Can result in fever, chills, muscle and joint aches, rash, blurred vision, swollen lymph nodes, or kidney problems; serum sickness is common when lymphocyte immune globulin is used alone for aplastic anemia, but fairly rare when it is combined with other drugs that suppress immunity.)
• Headaches, pain in the abdomen, diarrhea , nausea or vomiting, fluid retention, weakness, rapid heartbeats, or an abnormal increase in blood potassium (these side effects develop in more than a fifth of all patients during treatment)
• Uncommon side effects such as kidney damage, high blood pressure, heart failure, lethargy, abnormal sensations such as prickling in the skin, seizures, pulmonary edema, and adult respiratory distress syndrome
• Risk of developing lymphoma or leukemia, if the immune system is greatly suppressed for a long time

Side effects in pregnant or nursing women

The effects of this drug on an unborn child are unknown. Doctors are not sure if this drug reaches breast milk.

Methods of preventing or reducing side effects

Drugs such as antihistamines, acetaminophen, and corticosteroids can prevent or decrease some side effects, including fevers, chills, and allergic reactions. Antibiotics may help to prevent infections.

Interactions

Combining this drug with other medications that suppress the immune system (including chemotherapy ) can severely suppress immunity. Drugs that slow blood clotting, such as aspirin, can increase the risk of bleeding. Any drug that reduces the symptoms of an infection, including aspirin and acetaminophen, can increase the risk that a serious infection will go undetected.

See Also Myelosuppression; Immune response; Infection and sepsis; Neuropathy

Anna Rovid Spickler, D.V.M., Ph.D.

KEY TERMS

Adult respiratory distress syndrome (ARDS)

—A lung disease characterized by widespread lung abnormalities, fluid in the lungs, shortness of breath, and low oxygen levels in the blood.

Antibodies

—Proteins made by the immune system that attach to targeted molecules and cells.

Aplastic anemia

—Failure of the bone marrow to make enough blood cells.

Blood cells

—Cells found in the blood, including red blood cells that carry oxygen, white blood cells that fight infections, and platelets that help the blood to clot.

Bone marrow

—A group of cells and molecules found in the centers of some bones. It makes all of the cells found in the blood, including the cells involved in immunity.

Graft-versus-host disease (GVHD)

—A disease that develops when immune cells in transplanted bone marrow attack the body.

Immune system

—The cells and organs that defend the body against infections.

Pulmonary edema

—A disease characterized by excessive fluid in the lungs and difficulty breathing.

Sepsis

—An infection that has spread into the blood.

Serum sickness

—A type of allergic reaction against blood proteins. Serum sickness develops when the immune system makes antibodies against proteins that are not normally found in the body.

Skin test

—A test used to diagnose allergies.

T lymphocyte or T cell

—A type of white blood cell. Helper T cells aid other cells of the immune system, while cytotoxic T cells destroy abnormal body cells, including those that have been infected by a virus.

Thrombocytopenia

—Too few platelets in the blood.

Lymphocyte Typing

Definition

Lymphocyte typing focuses on identifying the numbers and relative percentages of lymphocytes in an individual's bloodstream. Lymphocytes, primarily T cells and B cells, are types of white blood cells, the underlying supports of the immune system in the bloodstream.

Purpose

Determining the numbers and relative percentages of T cells and B cells provides information on the state of a person's immune system. By comparing these values to normal numbers and percentages, the presence of disease and the side effects of certain drugs can be revealed. Lymphocyte typing can also show whether a person has been exposed to certain poisonous substances.

Description

To do a white blood cell count, a small amount of blood is drawn from a vein. The total number of white blood cells is calculated, either through microscopic examination of a blood smear or by using automated counting equipment. For a white blood cell count with differential, 100 white blood cells are counted and the proportion of each type is calculated. Since T cells and B cells have similar appearances, a differential can only give the proportion of lymphocytes in the blood, not the proportion of specific lymphocyte types.

For more specific information on B cells and T cells, it is necessary to divide the blood into its separate components. In this procedure, a tube of blood is placed in a centrifuge, a piece of equipment that spins the tube in circles at high speed. The force generated by the spinning causes the various elements in the bloodstream to settle at different levels of the tube.

The lymphocytes are extracted from the tube and treated with special dyes, or stains. Each stain is equipped with an antibody portion that adheres to a specific type of lymphocyte, such as a B cell or a T cell. The stains make the cells visible to an automated counting machine, called a flow cytometer. Based on the number of times the machine detects a particular stain, it can calculate the number of the associated cell type. This procedure can also be used to classify T cells and B cells into their subtypes.

Preparation

If possible, a person should avoid eating a heavy meal within hours of the test or engaging in strenuous exercise for the 24 hours preceding the blood test.

Normal results

In general, normal levels of white blood cells vary slightly by age and gender. Normal values are lower in children under the age of 15 and in young adults between the ages of 20 and 30. After age 30, men have slightly higher levels of white blood cells than women.

KEY TERMS

Immune system— The body's system of defenses against infectious diseases.

Lymphocytosis— A condition in which the number of lymphocytes increases above normal levels.

Lymphopenia— A condition in which the number of lymphocytes falls below normal levels.

White blood cell— A class of cells in the blood that form the foundation of the body's immune system.

Normal adult levels of white blood cells are 4,500-11,000 cells per microliter of blood. Lymphocytes account for approximately 25-45% of the total white blood cell count; the normal range is 1,000-4,800 lymphocytes per microliter of blood. Of the total lymphocytes, 60-80% are T cells and approximately 15% are B cells. (There are two other types of lymphocytes; natural killer and K-type; that constitute a minor proportion of the total lymphocyte numbers.)

Abnormal results

A higher-than-normal level of lymphocytes is called lymphocytosis. Lymphocytosis occurs if a person has a viral, bacterial, or other type of infection. It can also occur with certain blood disorders, such as leukemia.

Lower-than-normal levels of lymphocytes is called lymphopenia. Lymphopenia can be an indicator of certain cancers, bone marrow failure, or immune system deficiency. Medical treatments, such as chemotherapy and radiation therapy, can also deplete the body's supply of lymphocytes, as can exposure to poisonous substances.

Resources

BOOKS

Corbett, Jane Vincent. Laboratory Tests & Diagnostic Procedures with Nursing Diagnoses. 4th ed. Stamford: Appleton & Lange, 1996.

Turgeon, Mary Louise. Immunology & Serology in Laboratory Medicine. St. Louis: Mosby-Year Book, Inc., 1996.

Lymphocytic Choriomeningitis

Definition

Lymphocytic choriomeningitis (LCM) is a viral infection of the membranes surrounding the brain and spinal cord and of the cerebrospinal fluid.

Description

Lymphocytic choriomeningitis virus infection is relatively rare and recovery usually occurs spontaneously within a couple of weeks. Many cases are probably not even identified because the symptoms range from extremely mild to those resembling severe flu. A few patients develop symptoms of meningitis. In some rare cases, the LCM viral infection can spread throughout the central nervous system, and may even be fatal.

Causes and symptoms

LCM is caused by an arenavirus, which is an RNA virus and is a mild cousin in the family containing the much more threatening arenaviruses that cause hemmorrhagic fever. Humans acquire LCM virus from infected rodents by coming in contact with the animals or their excretions. Exposure to the virus is not as unlikely to occur as it seems, because the viral hosts can be common house mice and even pets, such as hamsters and chinchillas. Most cases of LCM occur in fall and winter, when mice seek warmth inside dwellings. Food and dust can become contaminated by the excretions of rodents infected with LCM virus. In 1997, French scientists alerted physicians to suspect LCM viral infection in people who had contact with Syrian hamsters.

The symptoms of LCM occur in two phases. The first (prodrome) stage can produce fever, chills, muscle aches, cough, and vomiting. In the second phase, characteristic meningitis symptoms of headache, stiff neck, listlessness, and nausea and vomiting may occur. In adults, complications are rare and recovery may even occur before the second phase.

The virus is not spread from person to person, except through pregnancy. LCM virus is one of the few viruses that can cross the placenta from mother to child during pregnancy and may be an underrecognized cause of congenital infection in newborns. Infection with cytomegalovirus, Toxoplasma gondii, or LCM virus can appear similar enough in infants to be confused when diagnosed. In cases that have been recognized among infants, LCM viral infection has a high mortality rate (about one-third of the babies studied died).

KEY TERMS

Prodrome— Symptom(s) experienced prior to the onset of a disease. For example, visual disturbances may precede and signal the onset of a migraine headache.

Diagnosis

LCM can be distinguished from bacterial meningitis by the history of prodrome symptoms and the period of time before meningitis symptoms begin, which is about 15-21 days for LCM.

Treatment

No antiviral agents exist for LCM virus. Treatment consists of supporting the patient and treating the symptoms until the infection subsides, generally within a few weeks.

lymphocyte A type of white blood cell (leucocyte) that has a large nucleus and little cytoplasm. Lymphocytes are formed in the lymph nodes and provide about a quarter of all leucocytes. They are important in the body's defence and are responsible for immune reactions as the presence of antigens stimulates them to produce antibodies. There are two populations of lymphocytes: B lymphocytes (see B cell), which produce circulating antibodies and are responsible for humoral immunity; and T lymphocytes (see T cell), which are responsible for cell-mediated immunity. See also killer cell.

lymphocyte (lim-foh-syt) n. a variety of white blood cell (leucocyte), present also in the lymph nodes, spleen, thymus gland, gut wall, and bone marrow. They are involved in immunity and can be subdivided into B-lymphocytes (or B-cells), which produce circulating antibodies, and T-lymphocytes, which are primarily responsible for cell-mediated immunity (see T-cell).
—lymphocytic adj.

lymphocyte Type of leucocyte (white blood cell) found in vertebrates. Produced in bone marrow, they are mostly found in the lymph and blood and around infected sites. In human beings, lymphocytes form c.25% of white blood cells and play an important role in combating disease. B-lymphocytes produce antibodies and T-lymphocytes maintain immunity. See also antibody

lym·pho·cyte / ˈlimfəˌsīt/ • n. Physiol. a form of small leukocyte (white blood cell) with a single round nucleus, occurring esp. in the lymphatic system. DERIVATIVES: lym·pho·cyt·ic / ˌlimfəˈsitik/ adj.

lymphocyte see blood ; immunity .

lymphocyte See LEUCOCYTE.