Immunologic deficiency syndromes

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Immunoglobulin Deficiency Syndromes

Immunoglobulin deficiency syndromes

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 2030 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.

Demographics

Primary immunoglobulin deficiency syndromes occur only rarely. Those that are X-linked occur more in males than females; other immunoglobulin deficiencies occur equally in both sexes. Detection of the syndromes usually occurs in childhood. Numbers of new cases of specific syndromes are difficult to estimate because many deficiencies go undiagnosed. Among the syndromes for which incidence rates are available are IgA deficiency (one in 500700), agammaglobulinemia (one in 50,000100,000), severe combined immunodeficiency or SCID (one in 100,000500,000), and common variable immunodeficiency or CVID (one in 50,000200,000).

Causes and symptoms

Primary immunoglobulin deficiencies are primarily the result of congenital defects that affect the development and function of B lymphocytes (B cells), the white cells that fight infection and disease. Defects can occur at two main points in the development of B-cells. First, B cells can fail to develop into antibody-producing cells. X-linked agammaglobulinemia 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 immunoglobulin classes. Failure to switch or failure to make a subclass can lead to immunoglobulin deficiency diseases. Defects in the thymus gland that manufactures T lymphocytes or defects in the T lymphocytes themselves can also result in reduced production of immunoglobulins.

Symptoms are frequent and so are persistent infections, particularly of the respiratory system. Frequent digestive disturbances and diarrhea may lead to malab-sorption of essential nutrients and failure to thrive . Children with primary immunoglobulin deficiency syndromes will exhibit some of the following characteristics:

  • signs of infection in the first days or weeks of life
  • a slow response to treatment
  • infection suppressed by appropriate treatment but not cured
  • common bacterial or viral organisms causing increasingly acute recurring infections
  • uncommon bacterial or viral organisms causing infection
  • multiple simultaneous infections at more than one site
  • delays in growth and development
  • development of unexpected complications such as anemias and chronic diseases

When to call the doctor

Parents should seek medical care from a pediatrician or family practitioner if their young child or teenager has frequent or persistent infections such as upper respiratory infections, or chronic cough , ear infections, sinusitis, asthma, or pneumonia. Sores that do not heal or recurring or long-lasting skin irritations may also be signs of reduced immune system functioning.

Diagnosis

An immunodeficiency disease is suspected when children become ill frequently, especially repeat illness caused by the same organisms. Diagnosis will begin with a detailed history of the child's illnesses (dates, duration, and infection site) and review of all prior medications and immunizations and results of diagnostic tests performed. Determining which immunoglobulins are present and which are absent or present in reduced amounts is critical for diagnosis. Diagnostic testing may include routine blood tests such as a complete blood count (CBC) and differential (peripheral blood smear) to evaluate overall health and determine the type and number of red cells, white cells, and platelets present in the blood. Tests or cultures may be performed to determine the type of bacteria or virus causing recurring infections. B lymphocytes and T lymphocytes may be quantified. When immunodeficiency is suspected, levels of the classes of immunoglobulins are measured in blood serum by using a clinical laboratory procedure called electrophoresis. This procedure both quantifies the amount of each antibody present and identifies the various classes and subclasses of antibodies. Deficiencies may be noted in one class or subclass or in combinations of antibodies. Genetic testing may be done to help identify the type of immunodeficiency disease.

Treatment

Immunoglobulin deficiency diseases cannot be cured, but treatment that replaces or boosts specific immunoglobulins can help support immune function in affected children. Immune serum, obtained from donated blood that contains adequate levels of IgG antibodies, may sometimes be transfused as a source of antibodies to boost the immune response, even though it may not contain all antibodies needed and may lack antibodies specific for some of the recurring infections. The preferred treatment is to give specific immunoglobulins intravenously (immunoglobulin intravenous therapy or IVIG) or subcutaneously. No replacement therapy is available for treating IgA deficiencies.

Treatment will also focus on controlling infections in immunodeficient children. Immunization against frequent infection can be achieved in some children by administering polysaccaride-protein conjugate vaccines shown to improve immune response in certain types of infection. Antibiotics are used routinely at the first sign of an infection to help eliminate infectious organisms. Antifungal drug therapy may be administered to treat fungus infections. Few drugs are effective against viral diseases, and each viral illness will be evaluated and treated differently, depending on the virus and the overall health of the child. Bone marrow transplantation may correct immunodefiency in some cases.

Alternative treatment

Several nutritional supplements are reported to help build the immune system. These include garlic (contains the essential trace element germanium), essential fatty acids (found in flax seed oil, evening primrose oil, and fish oils), sea vegetables such as kelp, acidophilus to supply natural bacteria in the digestive tract, and vitamins A and C, both powerful antioxidants that improve immune function and increase resistance to infection. Zinc is another nutrient essential to immune system functioning. Green drinks made with young barley are believed to cleanse the blood and supply chlorophyll and nutrients for tissue repair. Alcohol, certain prescription and over-the-counter drugs, and coffee and other caffeine drinks should be avoided. Stress is known to produce biochemicals that reduce white blood cell functioning, making it important to get sufficient sleep and reduce stress to help keep the immune system functioning. Therapeutic massage, yoga , and other types of stress reduction programs are available in most communities.

Nutritional concerns

Immune system function requires having certain essential nutrients and avoiding things that depress immunity. A diet that improves immune system functioning includes nutrients obtained as much as possible from whole foods such as fresh fruits and vegetables, whole grain breads and cereals, and brown rice and whole grain pasta for essential vitamins, minerals , and fiber. Such a diet also limits or eliminates refined foods.

Fish, fowl, and lean meats can be consumed in moderation. Sweets should be reduced or avoided.

Prognosis

Regular medical observation, treatment of symptoms, and appropriate immune system boosting usually produces a good result in children with immunodeficiencies. Prognosis is related to the immune system's ability to produce the specific antibodies that are missing or present in reduced amounts. Individuals with immunodeficiency syndromes may have a normal life span although a variety of complications can occur, including autoimmune, gastrointestinal, granulomatous, and malignant conditions as a result of progressive immune deficiency disorders and/or repeat infections.

Prevention

Immunodeficiency cannot be prevented; however, challenges to the immune system can be reduced and infections avoided in immunodeficient individuals. Immunoglobulin deficiencies require impeccable health maintenance and care, paying particular attention to good hygiene, balanced nutrition , sufficient rest, regular check ups and immunizations, and optimal dental care, as well as avoiding crowds and contact with other children or relatives with bacterial or virus infections.

Nutritional concerns

A healthy immune system can be maintained by providing essential nutrients through a good diet and regular supplementation. Parents can help assure that their children and teens have three nutritious, low-fat, high-fiber, whole-food meals a day (limiting or eliminating altogether refined or prepared foods and fast foods) and healthy snacks in between, such as nuts, fresh fruit, popcorn, raw veggies, and whole grain crackers with nut butters (if no allergies to peanuts or other nuts), naturally sweetened jellies, and low-fat cheeses. Vitamin supplements should include vitamins A, C, and E, valuable parts of the body's defense system that help to increase production of healthy white blood cells and to fight infection.

Parental concerns

Parents with immunoglobulin deficient children and teenagers will likely be concerned that their children are in frequent contact with schoolmates and friends, the common route to infection. When infection occurs frequently, it is important to remember that the pediatrician or family practitioner will have specific criteria and diagnostic tests for evaluating the child, identifying the immunodeficiency, and determining appropriate therapy. Meanwhile, parents can help keep their children away from crowds and avoid contact with other children or relatives with bacterial or virus infections.

KEY TERMS

Antibody A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Antigen A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.

Autosomal inheritance Inheritance involving any of the autosomes (22 pairs) and not involving sex-linked chromosomes X and Y.

Bacteria Singular, bacterium; tiny, one-celled forms of life that cause many diseases and infections.

Immunization A process or procedure that protects the body against an infectious disease by stimulating the production of antibodies. A vaccination is a type of immunization.

Immunoglobulin G (IgG) Immunoglobulin type gamma, the most common type found in the blood and tissue fluids.

Thymus gland An endocrine gland located in the upper chest just below the neck that functions as part of the lymphatic system. It coordinates the development of the immune system.

Virus A small infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell to reproduce.

Resources

BOOKS

Beers, Mark H., ed. Merck Manual of Medical Information, Second Home Edition. Whitehouse Station, NJ: Merck Research Laboratories, 2003.

Sompayrac, Lauren. How the Immune System Works. Oxford, UK: Blackwell, 2003.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Road, Atlanta, GA 30333. Web site: <www.cdc.gov>.

WEB SITES

Chin, Terry. "IgA and IgG Subclass Deficiency." eMedicine. Available online at <www.emedicine.com/ped/topic190.htm> (accessed January 14, 2005).

Makhoul, Issam. "Pure B-Cell Disorders." eMedicine. Available online at <www.emedicine.com/med/topic216.htm> (accessed January 14, 2005).

L. Lee Culvert Jacqueline L. Longe

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Culvert, L.; Longe, Jacqueline. "Immunoglobulin Deficiency Syndromes." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. 27 Aug. 2016 <http://www.encyclopedia.com>.

Culvert, L.; Longe, Jacqueline. "Immunoglobulin Deficiency Syndromes." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. (August 27, 2016). http://www.encyclopedia.com/doc/1G2-3447200305.html

Culvert, L.; Longe, Jacqueline. "Immunoglobulin Deficiency Syndromes." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Retrieved August 27, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3447200305.html

Common Variable Immunodeficiency

Common variable immunodeficiency

Definition

Common variable immunodeficiency (CVID) is a disorder of the immune system characterized by low levels of specific immunoglobulins, antibodies produced by the immune system to fight infection or disease. In CVID, immunoglobulin G (IgG) antibodies, one of several classes of antibodies, are either absent or produced in lower than normal numbers. Children who have this disorder are subject to recurring infections and may not respond appropriately to immunization. In some children, levels of the four types of IgG may be out of balance, a condition that has been associated with autoimmune diseases.

Description

The function of the immune system is to respond to organisms and substances that invade the body, such as bacteria, viruses, fungi, parasites, and toxins, by producing antibodies against them. Antibodies are specific proteins (immunoglobulins) manufactured by the immune system to bind to corresponding molecules (antigens) on the cell surfaces of foreign organisms in an attempt to make them harmless. This antigen/antibody reaction is the body's way of protecting itself from invasion and possible illness. Immunodeficiency means that the immune system is deficient in one or more of its components and is unable to respond effectively to disease-producing organisms that invade the body. IgG antibodies, the specific immunoglobulins absent or reduced in CVID, are targeted at bacterial organisms, viruses, and certain toxins.

Individuals with CVID will typically have frequent infections, especially repeat infections caused by the same organism. Recurring infections are an indication that the immune system is not responding normally and that immunity to reinfection has not developed. Surprisingly, people with CVID will usually have a normal number of B cells, the type of white blood cells (B-cell lymphocytes) that make antibodies to fight infection. However, the B cells will either be lacking one of the necessary IgG antibodies (IgG subclasses IgG1, IgG2, IgG3, and IgG4) on their surfaces or will have reduced amounts of one or more subclasses, making the B cells incapable of responding appropriately to microorganisms. Although the total IgG level may be normal, the imbalance in the types of IgG antibodies makes the B cells unprepared to fight all types of infection. The toxin associated with tetanus , for example, is attacked by IgG1 and IgG3 antibodies; reduced percentages of either immunoglobulin subclass on a child's cells will leave the child unprotected against that specific toxin. Similarly, frequent sinus infections may result from deficiencies of IgG2 and IgG3.

CVID may include deficiencies in other immunoglobulins as well, such as IgA and IgM deficiencies, although these deficiencies are more frequently associated with a group of other primary immunoglobulin deficiencies (agammaglobulinemia, severe combined immunodeficiency , and others). Other components of the immune system may be normal in CVID. T-cell lymphocytes, the type of white cells responsible for cellular immunity, are usually manufactured at normal levels in the same individuals who have CVID, although certain cell signal components may be lacking.

Autoimmune diseases such as autoimmune hemolytic anemia (AIHA), immune thrombocytopenia purpura (ITP), rheumatoid arthritis, autoimmune thyroiditis, and systemic lupus erythematosus are sometimes associated with CVID. These conditions develop in CVID as a result of the production of autoantibodies (antibodies directed against the body's own tissue). The term variable applies to this range of possible complications, which also includes gastrointestinal disorders as well as certain cancers, such as lymphomas and leukemias.

Demographics

Common variable immunodeficiency is believed to affect one in 50,000 to 200,000 individuals although it is not always diagnosed, and exact numbers of cases in the population cannot be accurately determined.

Causes and symptoms

The cause of common variable immunodeficiency was as of 2004 not known, although some forms seem to be inherited. The group of deficiencies is believed to be heterogeneous, that is, having widely varying characteristics among those affected.

CVID usually appears in children after the age of ten. The primary symptom is the presence of recurring infections that tend to be chronic rather than acute. Most children have had at least one episode of pneumonia caused by Streptococcus pneumoniae. Some children may also have frequent digestive disturbances and diarrhea that can lead to improper absorption of nutrients and malnourishment, occurring most commonly in IgA deficiency.

When to call the doctor

Young children and teenagers who are having recurrent infections, particularly infections of the same type such as frequent upper respiratory infection or chronic chest symptoms, ear infections, sinusitis, asthma , or pneumonia should be evaluated by a pediatrician or family practitioner.

Diagnosis

Children are typically diagnosed after age ten, but some immunoglobulin subclass deficiencies appear between ages one and three and are diagnosed after repeat cases of sinusitis, pneumonia, bacteremia, bronchiectasis, or diarrhea and malabsorption. A history of the child's illnesses and immunizations will be obtained, and the doctor will determine the child's general pattern of growth and development. Diagnostic testing may include routine blood tests such as a complete blood count (CBC) and differential (peripheral blood smear) to evaluate overall health and determine the type and number of red cells, white cells, and platelets in the blood. B lymphocytes and T lymphocytes may be quantified. An erythrocyte sedimentation rate (ESR) may be done to determine if inflammation is present. Blood chemistries may be performed to evaluate overall organ system functioning. If immunodeficiency is suspected, the primary diagnostic test that will distinguish common variable immunodeficiency from other types of immune system dysfunction is a reduced level of IgG immunoglobulins or IgG antibody subclasses, despite a relatively normal number of B cells. Serum immunoglobulin levels are measured in the clinical laboratory by a procedure called electrophoresis. This procedure both quantifies the amount of each antibody present and identifies the various classes and subclasses of antibodies. Deficiencies may be noted in one class or subclass or in combinations of IgG, IgM and IgA antibodies. Genetic testing may be done to rule out other types of immunodeficiency disease.

Not all children who have repeat infections are immunodeficient. Doctors tell the difference by evaluating the child's history and development. A normal child who most likely does not need further examination or diagnostic testing will have the following characteristics:

  • no history of deep infection at multiple sites, even though repeat upper respiratory infections or ear infections may occur
  • overall normal growth and body functions
  • generally good health and normal functioning between infections
  • no known family history of immune system deficiencies

The type of organism causing repeat infection can be a clue to which immunoglobulins are deficient. Therefore, when infection is present in suspected cases of common variable immunodeficiency, it may be important to identify the bacteria or virus causing the illness. Diagnostic tests may include performing a culture on material from the nose, throat, a wound, blood, or urine of the affected child.

Treatment

As of 2004 no specific treatment cured common variable immunodeficiency; each child is treated according to the individual clinical condition, the symptoms presented, and the antibody subclasses shown to be absent or deficient. Treatment is aimed generally at boosting the body's immune response and preventing or controlling infections. Immune serum, obtained from donated blood that contains adequate levels of IgG antibodies, may sometimes be transfused as a source of antibodies to boost the immune response, even though it may not contain all the antibodies the child needs and may lack antibodies specific for some of the recurring infections. The preferred treatment is to give immunoglobulins intravenously (immunoglobulin intravenous therapy or IVIG) or intramuscularly (IMIG) if specific antibody deficiencies are found; this is not usually done to boost IgA levels, however, because of the possible presence of anti-IgA antibodies that could cause an unwanted reaction. Immunization against frequent infection can be achieved in some children by administering polysaccaride-protein conjugate vaccines shown to improve immune response in certain types of infection. Antibiotics are used routinely at the first sign of an infection to help eliminate infectious organisms.

Alternative treatment

Several nutritional supplements are reported to help build the immune system. These include garlic (contains the essential trace element germanium), essential fatty acids (abundant in flax seed oil, evening primrose oil, and fish oils), sea vegetables such as kelp, acidophilus to supply natural bacteria in the digestive tract, and vitamins A and C, both powerful antioxidants that improve immune function and increase resistance to infection. Zinc is another nutrient essential to immune system functioning. Green drinks made with young barley are believed to cleanse the blood and supply chlorophyll and nutrients for tissue repair. Alcohol, medications, drugs, coffee, and other caffeine drinks should be avoided. Stress is known to produce biochemicals that reduce white blood cell functioning; therefore, it is important for the child to get sufficient sleep and reduce stress to help improve immune system functioning. Therapeutic massage, yoga , and other types of stress reduction programs are available in most communities.

Prognosis

Regular medical observation, treatment of symptoms, and appropriate immune system boosting usually produces a good result in children with common variable immunodeficiency. In some children, delayed maturation of certain IgG subclasses will make the condition a temporary one that corrects itself as more typical levels of the IgG antibodies develop. In other children, prognosis is related to the immune system's ability to produce specific antibodies. Individuals with common variable immunodeficiency usually have a normal life span although a variety of complications can occur, including autoimmune, gastrointestinal, granulomatous, and malignant conditions as a result of progressive immune deficiency.

Prevention

The disorder cannot be prevented, but parents can take precautions to prevent the recurrent infections commonly associated with immunodeficiency. For example, practicing good hygiene and providing optimum nutrition are important for helping children avoid contact with infectious organisms and to develop resistance against them. Avoiding crowds and staying away from other children or relatives who have active infections is another important way to avoid challenges to the immune system.

Nutritional concerns

Maintaining a healthy immune system requires essential nutrients that can be provided through a good diet and regular supplementation. A diet to improve immune system functioning includes fresh fruits and vegetables, as many eaten raw as possible to provide necessary enzymes; whole grain cereals, brown rice, and whole grain pasta for essential vitamins, minerals , and fiber; and non-meat sources of protein such as nuts, seeds, tofu, legumes (beans), and eggs. Fish, fowl, and lean meats can be consumed in small amounts. Sweets, especially if sweetened with refined sugars, should be reduced or avoided altogether. Vitamin supplements should include vitamins A, C, and E, which are all valuable parts of the body's defense system, helping to increase the production of healthy white blood cells and to fight infection.

Parental concerns

Parents are aware that school-age children and teenagers are in frequent contact with their peers in school and at play , and infections commonly spread. In this situation, when infection occurs frequently, it is important to remember that not all children or teens who have repeat infections are immunodeficient and that the pediatrician or family practitioner will have specific criteria and diagnostic tests to rule out common variable immunodeficiency.

KEY TERMS

Antibody A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Antigen A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.

Bacteria Singular, bacterium; tiny, one-celled forms of life that cause many diseases and infections.

Culture A test in which a sample of body fluid is placed on materials specially formulated to grow microorganisms. A culture is used to learn what type of bacterium is causing infection.

Immunization A process or procedure that protects the body against an infectious disease by stimulating the production of antibodies. A vaccination is a type of immunization.

Immunoglobulin G (IgG) Immunoglobulin type gamma, the most common type found in the blood and tissue fluids.

Vaccination Another word for immunization.

Vaccine A substance prepared from a weakened or killed microorganism which, when injected, helps the body to form antibodies that will prevent infection by the natural microorganism.

Virus A small infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell to reproduce.

See also Immunodeficiency syndromes; HIV infection and AIDS.

Resources

BOOKS

Sompayrac, Lauren. How the Immune System Works. Oxford, UK: Blackwell, 2003.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Road, Atlanta, GA 30333. Web site: <www.cdc.gov>.

WEB SITES

"Understanding the Immune System." Science behind the News. Available online at <http://press2.nci.nih.gov/sciencebehind/immune/immune.00htm> (accessed December 8, 2004).

L. Lee Culvert John T. Lohr, PhD

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Culvert, L.; Lohr, John. "Common Variable Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. 27 Aug. 2016 <http://www.encyclopedia.com>.

Culvert, L.; Lohr, John. "Common Variable Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. (August 27, 2016). http://www.encyclopedia.com/doc/1G2-3447200143.html

Culvert, L.; Lohr, John. "Common Variable Immunodeficiency." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Retrieved August 27, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3447200143.html

DiGeorge Syndrome

DiGeorge syndrome

Definition

DiGeorge syndrome is a rare congenital disease that affects an infant's immune system and that is due to a large deletion from chromosome 22. The syndrome is marked by absence or underdevelopment of the thymus and parathyroid glands. It is named for the pediatrician who first described it in 1965.

Normally the thymus gland is located below the thyroid gland in the neck and front of the chest and is the primary gland of the lymphatic system, which is necessary for normal functioning of the immune system. The parathyroid glands, located on the sides of the thyroid gland, are responsible for maintenance of normal levels of calcium in the blood. In children with DiGeorge syndrome, the thymus and parathyroid glands are missing or undeveloped. The symptoms of this disorder vary, depending on the extent of missing thymus and parathyroid tissue. The primary problem for children who survive with DiGeorge syndrome is repeated infections due to a defective immune system.

DiGeorge syndrome is sometimes described as a "CATCH 22" disorder, so named because of their characteristicscardiac defects (C), abnormal facial features (A), thymus underdevelopment (T), cleft palate (C), and hypocalcemia due to hypoparathyroidism(H)all resulting from deletion of portions of chromosome 22. Specific facial features associated with DiGeorge syndrome include low-set ears, wide-set eyes, a small jaw, and a short groove in the upper lip.

DiGeorge syndrome is also called congenital thymic hypoplasia, or third and fourth pharyngeal pouch syndrome, because the congenital abnormalities occur in areas known as the third and fourth pharyngeal pouches, which later develop into the thymus and parathyroid glands.

Demographics

The prevalence of DiGeorge syndrome, is debated; estimates have ranged from one in 4,000 to one in 6,395. Because the symptoms caused by the chromosomal abnormality vary somewhat from child to child, the syndrome probably occurs much more often than was previously thought. In the United States, autopsy studies for DiGeorge syndrome accounted for 0.7 percent of 3469 postmortem examinations in the Seattle, Washington, area over a period of 25 years. Internationally, the incidence of DGS was estimated to be one case per 20,000 persons in Germany and one case per 66,000 persons in Australia. However, with the advent of fluorescence in situ hybridization (FISH) techniques to detect monosomy 22 and the inclusion of related syndromes, more recent estimates place the incidence of DiGeorge syndrome in the range of one case per 3,000 persons.

No major difference is noted in the incidence of DiGeorge syndrome between males and females. The syndrome also appears to be equally common in all racial and ethnic groups.

Causes and symptoms

DiGeorge syndrome is caused either by inheritance of a defective chromosome 22 or by a new defect in chromosome 22 in the fetus. The type of defect that is involved is called deletion. A deletion occurs when the genetic material in the chromosomes does not recombine properly during the formation of sperm or egg cells. The deletion means that several genes from chromosome 22 are missing in children with DiGeorge syndrome. According to a 1999 study, 6 percent of children with DiGeorge syndrome inherited the deletion from a parent, while 94 percent had a new deletion.

The loss of the genes in the deleted material means that the baby's third and fourth pharyngeal pouches fail to develop normally during the twelfth week of pregnancy. This developmental failure results in a completely or partially absent thymus gland and parathyroid glands. In addition, 74 percent of fetuses with DiGeorge syndrome have severe heart defects. The child is born with a defective immune system and an abnormally low level of calcium in the blood.

These defects usually become apparent within 48 hours of birth. The infant's heart defects may lead to heart failure, or there may be seizures and other evidence of a low level of calcium in the blood (hypocalcemia).

When to call the doctor

Because the immune system of a child with DiGeorge syndrome is defective, a doctor should be consulted at any signs of illness or disease.

Diagnosis

Diagnosis of DiGeorge syndrome can be made by ultrasound examination around the eighteenth week of pregnancy, when abnormalities in the development of the heart or the palate can be detected. Another technique that is used to diagnose the syndrome before birth is called fluorescence in situ hybridization, or FISH. This technique uses DNA probes from the DiGeorge region on chromosome 22. FISH can be performed on cell samples obtained by amniocentesis as early as the fourteenth week of pregnancy. It confirms about 95 percent of cases of DiGeorge syndrome.

If the mother has not had prenatal testing, the diagnosis of DiGeorge syndrome is sometimes suggested by the child's facial features at birth. The child is also born with a defective immune system and an abnormally low level of calcium in the blood. These defects usually become apparent within 48 hours after birth. The infant's heart defects may lead to heart failure, or there may be seizures and other evidence of a low level of calcium in the blood. The doctor may make the diagnosis of DiGeorge syndrome during heart surgery when he or she notices the absence or abnormal location of the thymus gland. The diagnosis can be confirmed by blood tests for calcium, phosphorus, and parathyroid hormone levels and by the sheep cell test for immune function.

Treatment

Hypocalcemia

Hypocalcemia in a child with DiGeorge syndrome is unusually difficult to treat. Infants are usually given calcium and vitamin D by mouth. Severe cases have been treated by transplantation of fetal thymus tissue or bone marrow.

Heart defects

Infants with life-threatening heart defects are treated surgically.

Defective immune function

Children with DiGeorge syndrome should be kept away from crowds or other sources of infection. They should not be immunized with vaccines made from live viruses or given corticosteroids.

Nutritional concerns

Children with DiGeorge syndrome should be kept on low-phosphorus diets.

Prognosis

The prognosis is variable; many infants with DiGeorge syndrome die from overwhelming infection, seizures, or heart failure within the first year. A one-month mortality rate of 55 percent and a six-month mortality rate of 86 percent has been reported due to congenital heart disease . Advances in heart surgery indicate that the prognosis is most closely linked to the severity of the heart defects and the partial presence of the thymus gland. In most children who survive, the number of T cells, a type of white blood cell, in the blood rises spontaneously as they mature. Survivors are likely to be mentally retarded, however, with mild to moderate learning disabilities, and to have other developmental difficulties, including short stature as well as psychiatric problems in later life

Prevention

Genetic counseling and testing is recommended for a person with DiGeorge syndrome who becomes pregnant, because the disorder can be detected prior to birth. Although most children with DiGeorge syndrome do not inherit the chromosome deletion from their parents, they have a 50 percent chance of passing the deletion on to their own children. Parents should be screened, however, to see if they are carriers, even though inheritance of DiGeorge syndrome is rare.

Because of an association between DiGeorge syndrome and fetal alcohol syndrome , pregnant women should avoid drinking alcoholic beverages.

Parental concerns

Recurrent infections are a major problem in children with DiGeorge syndrome and an important cause of later mortality. Therefore, prevention of infections must be a high priority.

KEY TERMS

Amniocentesis A procedure performed at 16-18 weeks of pregnancy in which a needle is inserted through a woman's abdomen into her uterus to draw out a small sample of the amniotic fluid from around the baby for analysis. Either the fluid itself or cells from the fluid can be used for a variety of tests to obtain information about genetic disorders and other medical conditions in the fetus.

Chromosome A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.

Congenital Present at birth.

Deletion The absence of genetic material that is normally found in a chromosome. Often, the genetic material is missing due to an error in replication of an egg or sperm cell.

Hypocalcemia A condition characterized by an abnormally low level of calcium in the blood.

Hypoplasia An underdeveloped or incomplete tissue or organ usually due to a decrease in the number of cells.

T cell A type of white blood cell that is produced in the bone marrow and matured in the thymus gland. It helps to regulate the immune system's response to infections or malignancy.

Resources

BOOKS

Moore, Keith L., et al. Before We Are Born: Essentials of Embryology and Birth Defects. Kent, UK: ElsevierHealth Sciences Division, 2002.

PERIODICALS

Schinke, M., and S. Izumo. "Deconstructing DiGeorge Syndrome." Nature Genet 27 (2001): 238240.

ORGANIZATIONS

Chromosome 22 Central. 237 Kent Avenue, Timmins, Ontario. Web site: <www.c22c.org>.

Immune Deficiency Foundation. 40 West Chesapeake Avenue, Towson, MD 21230. Web site: <http://primaryimmune.org>.

WEB SITES

Guduri, Sridhar, et al. "DiGeorge Syndrome." emedicine, August 14, 2004. Available online at <www.emedicine.com/med/topic567.htm> (accessed November 17, 2004).

Judith Sims, MS Rebecca J. Frey PhD

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Sims, Judith; Frey, Rebecca. "DiGeorge Syndrome." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. 27 Aug. 2016 <http://www.encyclopedia.com>.

Sims, Judith; Frey, Rebecca. "DiGeorge Syndrome." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. (August 27, 2016). http://www.encyclopedia.com/doc/1G2-3447200192.html

Sims, Judith; Frey, Rebecca. "DiGeorge Syndrome." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Retrieved August 27, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3447200192.html

DiGeorge Syndrome

DiGeorge Syndrome

Definition

DiGeorge syndrome (also called 22q11 deletion syndrome, congenital thymic hypoplasia, or third and fourth pharyngeal pouch syndrome) is a birth defect that is caused by an abnormality in chromosome 22 and affects the baby's immune system. The disorder is marked by absence or underdevelopment of the thymus and parathyroid glands. It is named for Angelo DiGeorge, the pediatrician who first described it in 1965. Some researchers prefer to call it DiGeorge anomaly, or DGA, rather than DiGeorge syndrome, on the grounds that the defects associated with the disorder represent the failure of a part of the human embryo to develop normally rather than a collection of symptoms caused by a single disease.

Description

The prevalence of DiGeorge syndrome is debated; the estimates range from 1:4000 to 1:6395. Because the symptoms caused by the chromosomal abnormality vary somewhat from patient to patient, the syndrome probably occurs much more often than was previously thought. DiGeorge syndrome is sometimes described as one of the "CATCH 22" disorders, so named because of their characteristicscardiac defects, abnormal facial features, thymus underdevelopment, cleft palate, and hypocalcemiacaused by a deletion of several genes in chromosome 22. The specific facial features associated with DiGeorge syndrome include low-set ears, wide-set eyes, a small jaw, and a short groove in the upper lip. The male/female ratio is 1:1. The syndrome appears to be equally common in all racial and ethnic groups.

Causes and symptoms

DiGeorge syndrome is caused either by inheritance of a defective chromosome 22 or by a new defect in chromosome 22 in the fetus. The type of defect that is involved is called deletion. A deletion occurs when the genetic material in the chromosomes does not recombine properly during the formation of sperm or egg cells. The deletion means that several genes from chromosome 22 are missing in DiGeorge syndrome patients. Although efforts have been made in the early 2000s to identify individual candidate genes for DGA, it appears that a combination of several genes in the deleted area is responsible for the disorder. Detailed genetic mapping of chromosome 22 has, however, identified a so-called DiGeorge critical region (DGCR), which has been completely sequenced.

According to a 1999 study, 6% of children with DiGeorge syndrome inherited the deletion from a parent, while 94% had a new deletion. Other conditions that are associated with DiGeorge syndrome are diabetes (a condition where the pancreas no longer produces enough insulin) in the mother and fetal alcohol syndrome (a pattern of birth defects, and learning and behavioral problems affecting individuals whose mothers consumed alcohol during pregnancy ). Other chromosomal abnormalities that have been found in patients diagnosed with DGA include deletions on chromosomes 10p13, 17p13, and 18q21.

The loss of the genes in the deleted material means that the baby's third and fourth pharyngeal pouches fail to develop normally during the twelfth week of pregnancy. This developmental failure results in a completely or partially absent thymus gland and parathyroid glands. In addition, 74% of fetuses with DiGeorge syndrome have severe heart defects. The child is born with a defective immune system and an abnormally low level of calcium in the blood. Some children with DGA are also born with malformations of the genitals or urinary tract.

These defects usually become apparent within 48 hours of birth. The infant's heart defects may lead to heart failure, or there may be seizures and other evidence of a low level of calcium in the blood (hypocalcemia ).

DiGeorge syndrome is also associated with an increased risk of autoimmune disorders. Cases have been reported of DGA in association with Graves' disease, immune thrombocytopenic purpura, juvenile rheumatoid arthritis, and severe eczema.

Diagnosis

Diagnosis of DiGeorge syndrome can be made by ultrasound examination around the eighteenth week of pregnancy, when abnormalities in the development of the heart or the palate can be detected. Another technique that is used to diagnose the syndrome before birth is called fluorescence in situ hybridization, or FISH. This technique uses DNA probes from the DiGeorge region on chromosome 22. FISH can be performed on cell samples obtained by amniocentesis as early as the fourteenth week of pregnancy. It confirms about 95% of cases of DiGeorge syndrome.

If the mother has not had prenatal testing, the diagnosis of DiGeorge syndrome is sometimes suggested by the child's facial features at birth. In other cases, the doctor makes the diagnosis during heart surgery when he or she notices the absence or abnormal location of the thymus gland. The diagnosis can be confirmed by blood tests for calcium, phosphorus, and parathyroid hormone levels, and by the sheep cell test for immune function.

Treatment

Hypocalcemia

Hypocalcemia in DiGeorge patients is unusually difficult to treat. Infants are usually given calcium and vitamin D by mouth. Severe cases have been treated by transplantation of fetal thymus tissue or bone marrow.

Heart defects

Infants with life-threatening heart defects are treated surgically.

Defective immune function

Children with DiGeorge syndrome should be kept on low-phosphorus diets and kept away from crowds or other sources of infection. They should not be immunized with vaccines made from live viruses or given corticosteroids.

Prognosis

The prognosis is variable; many infants with DiGeorge syndrome die from overwhelming infection, seizures, or heart failure within the first year. One study of a series of 558 patients reported 8% mortality within six months of birth, with heart defects accounting for all but one of the deaths. Infections resulting from severe immune deficiency are the second most common cause of death in patients with DGA. Advances in heart surgery indicate that the prognosis is most closely linked to the severity of the heart defects and the partial presence of the thymus gland. In most children who survive, the number of T cells, a type of white blood cell, in the blood rises spontaneously as they mature. Survivors are likely to be mentally retarded, however, and to have other developmental difficulties, including seizures or other psychiatric and neurological problems in later life.

Prevention

Genetic counseling is recommended for parents of children with DiGeorge syndrome because the disorder can be detected prior to birth. Although most children with DiGeorge syndrome did not inherit the chromosome deletion from their parents, they have a 50% chance of passing the deletion on to their own children.

KEY TERMS

Deletion A genetic abnormality in which a segment of a chromosome is lost. DiGeorge syndrome is caused by a deletion on human chromosome 22.

Fetal alcohol syndrome A cluster of birth defects that includes abnormal facial features and mental retardation, caused by the mother's consumption of alcoholic beverages during pregnancy.

Fluorescence in situ hybridization (FISH) A technique for diagnosing DiGeorge syndrome before birth by analyzing cells obtained by amniocentesis with DNA probes. FISH is about 95% accurate.

Hypocalcemia An abnormally low level of calcium in the blood.

Hypoplasia A deficiency or underdevelopment of a tissue or body structure.

T cells A type of white blood cell produced in the thymus gland. T cells are an important part of the immune system. Infants born with an underdeveloped or absent thymus do not have a normal level of T cells in their blood.

Because of the association between DiGeorge syndrome and fetal alcohol syndrome, pregnant women should avoid drinking alcoholic beverages.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Immunodeficiency Diseases." Section 12, Chapter 147 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

McDonald-McGinn, Donna M., et al. 22q11 Deletion Syndrome. Philadelphia: The Children's Hospital of Philadelphia, 1999.

PERIODICALS

Guduri, Sridhar, MD, and Iftikhar Hussain, MD. "DiGeorge Syndrome." eMedicine May 28, 2002. http://www.emedicine.com/med/topic567.htm.

Verri, A., P. Maraschio, K. Devriendt, et al. "Chromosome 10p Deletion in a Patient with Hypoparathyroidism, Severe Mental Retardation, Autism and Basal Ganglia Calcifications." Annales de génétique 47 (July-September 2004): 281-287.

Yatsenko, S. A., A. N. Yatsenko, K. Szigeti, et al. "Interstitial Deletion of 10p and Atrial Septal Defect in DiGeorge 2 Syndrome." Clinical Genetics 66 (August 2004): 128-136.

ORGANIZATIONS

Canadian 22q Group. 320 Cote Street Antoine, West Montreal, Quebec H3Y 2J4.

Chromosome Deletion Outreach, Inc. P.O. Box 724, Boca Raton, FL 33429-0724. (888) 236-6680.

International DiGeorge/VCF Support Network, c/o Family Voices of New York. 46 1/2 Clinton Avenue, Cortland, NY 13045. (607) 753-1250.

National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100. Fax: (203) 798-2291. http://www.rarediseases.org.

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Immunoglobulin Deficiency Syndromes

Immunoglobulin Deficiency Syndromes

Definition

Immunoglobulin deficiency syndromes are a group of immunodeficiency disorders in which the patient has a 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.

  • 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.

Causes and 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 agammaglobulinemia 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 that 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.

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.

Treatment

Immunodeficiency diseases cannot 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 impeccable health maintenance and care, paying particular attention to optimal dental care, in order to stay in good health.

Resources

BOOKS

Berkow, Robert, editor. Merck Manual of Medical Information. Whitehouse Station, NJ: Merck Research Laboratories, 1997.

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Common Variable Immunodeficiency

Common Variable Immunodeficiency

Definition

Common variable immunodeficiency is an immunodeficiency disorder characterized by a low level of antibodies. Patients with this disease are subject to recurring infections.

Description

Immunodeficiency means that the immune system is deficient in one or more of its components and is unable to respond effectively. Common variable immunodeficiency is the most common of the immunodeficiency disorders. Patients with this disease have frequent infections, especially those caused by the same microorganism. Recurring infections are an indication that the immune system is not responding normally and developing immunity to reinfection. Patients with common variable immunodeficiency have a normal number of B cells, the lymphocytes that make antibodies. In approximately one-third of these patients, the number of B cells in the blood that have IgG antibodies on their surface is lower than normal, but there are normal numbers of B cells in their bone marrow. B cells with IgG antibodies on their surface are capable of responding to microorganisms. The lack of IgG on the surface of the B cells means that they are not prepared to fight infection. The T-cell lymphocytes, those cells responsible for cellular immunity, are usually normal, although some cell signal components may be lacking.

Causes and symptoms

The cause of common variable immunodeficiency is not known, although some forms seem to be hereditary. The main symptom is recurring infections that tend to be chronic rather than acute. Patients may also develop diarrhea and, as a consequence of the diarrhea, do not absorb food efficiently. This can lead to malnourishment that can aggravate the disorder. Common variable immunodeficiency normally appears in children after the age of 10. Autoimmune disorders such as rheumatoid arthritis, thyroiditis, and systemic lupus erythematosus and certain cancers such as lymphomas and leukemias may be associated with common variable immunodeficiency.

Diagnosis

As is true of most immunodeficiency disorders, one of the first signs that the patient has the condition is recurrent infections. Patients with common variable immunodeficiency are subject to recurrent infections, especially those caused by microbes that don't normally cause disease in normal persons. The main diagnostic test that distinguishes common variable immunodeficiency from other immunodeficiency diseases is the low antibody level despite the normal number of B cells. Antibody levels are tested in the serum by a procedure called electrophoresis. This procedure both quantifies the amount of antibody present and identifies the various classes of antibodies. The main class of antibody for fighting infectious diseases is IgG.

Treatment

There is no treatment that will cure the disorder. Treatment for common variable immunodeficiency aims at boosting the body's immune response and preventing or controlling infections. Immune serum, obtained from donated blood, is given as a source of antibodies to boost the immune response. Immune serum is obtained from donated blood. It contains whatever antibodies the donors had in their blood. Consequently, it may not contain all the antibodies that the patient needs and may lack antibodies specific for some of the recurring infections that these patients suffer. Antibiotics are used routinely at the first sign of an infection to help the patient eliminate infectious microorganisms.

Prognosis

With good medical care, people with common variable immunodeficiency usually have a normal life span.

Prevention

The disease itself cannot be prevented, but patients and their families can take precautions to prevent the recurrent infections commonly associated with it. For example, good hygiene and nutrition are important, as is avoiding crowds or other people who have active infections.

Resources

BOOKS

Abbas, Abul K., Andrew H. Lichtman, and Jordan S. Pober. Cellular and Molecular Immunology. 3rd ed. Philadelphia: W. B. Saunders Co., 1997.

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