Immunodeficiency disorders involve malfunction of the immune system, resulting in infections that develop and recur more frequently, are more severe, and last longer than usual.
Immunodeficiency disorders usually result from use of a medication or from a long-lasting serious disorder (such as cancer) but occasionally are inherited.
People usually have frequent, unusual, or unusually severe or prolonged infections and may develop an autoimmune disorder or cancer.
Doctors suspect immunodeficiency based on symptoms and do blood tests to identify the particular disorder.
People may be given antimicrobial drugs (such as antibiotics) to prevent and treat infections.
Immune globulin may be given if there are too few antibodies (immunoglobulins) or they are not functioning normally.
For some severe immunodeficiency disorders, stem cell transplantation is sometimes done.
(See also Overview of the Immune System.)
Immunodeficiency disorders impair the immune system’s ability to defend the body against foreign or abnormal cells that invade or attack it (such as bacteria, viruses, fungi, and cancer cells). As a result, unusual bacterial, viral, or fungal infections or lymphomas or other cancers may develop.
Some people who have an immunodeficiency disorder also have an autoimmune disorder (such as immune thrombocytopenia). In an autoimmune disorder, the immune system attacks the body's own tissues. Sometimes the autoimmune disorder develops before the immunodeficiency causes any symptoms.
There are 2 types of immunodeficiency disorders:
Primary: These disorders are usually present at birth and are genetic disorders that are usually hereditary. They typically become evident during infancy or childhood. However, some primary immunodeficiency disorders (such as common variable immunodeficiency) are not recognized until adulthood. There are numerous primary immunodeficiency disorders. All are relatively rare.
Secondary: These disorders generally develop later in life and often result from use of certain medications or from another disorder, such as diabetes or human immunodeficiency virus (HIV) infection. They are more common than primary immunodeficiency disorders.
Some immunodeficiency disorders shorten life span. Others persist throughout life but do not affect life span, and a few resolve with or without treatment.
Causes of Immunodeficiency Disorders
Primary immunodeficiency
Primary immunodeficiency disorders may be caused by mutations, sometimes in a specific gene. If the mutated gene is on the X (sex) chromosome, the resulting disorder is called an X-linked disorder. X-linked disorders occur more often in boys. About 60% of people with primary immunodeficiency disorders are male.
Primary immunodeficiency disorders are classified by which part of the immune system is affected:
Humoral immunity, which involves B cells (lymphocytes), a type of white blood cell that produces antibodies (immunoglobulins)
Cellular immunity, which involves T cells (lymphocytes), a type of white blood cell that helps identify and destroy foreign or abnormal cells
Both humoral and cellular immunity (B cells and T cells)
Phagocytes (cells that ingest and kill microorganisms)
Complement proteins (proteins that help immune cells kill bacteria and identify foreign cells to destroy)
The affected component of the immune system may be missing, reduced in number, or abnormal and malfunctioning.
Problems with B cells are the most common primary immunodeficiency disorders, accounting for more than half.
Some Primary Immunodeficiency Disorders
Part of the Immune System That Is Affected | Disorder |
|---|---|
Humoral immunity: Problems with B cells (lymphocytes) and their production of antibodies | Common variable immunodeficiency Deficiency of a specific antibody (selective immunoglobulin deficiency), such as IgA deficiency |
Cellular immunity: Problems with T cells (lymphocytes) | |
Combined humoral and cellular immunity: Problems with B and T cells | Hyperimmunoglobulinemia E syndrome |
Phagocytes: Problems with the movement or killing activity of these cells | Chédiak-Higashi syndrome (rare) |
Complement proteins: Deficiency of complement proteins | Complement component 1 (C1) inhibitor deficiency (hereditary angioedema) C2, C3, C4, C5, C6, C7, C8 and/or C9 deficiency |
Secondary immunodeficiency disorders
These disorders can result from
Prolonged (chronic) and/or serious disorders such as diabetes or cancer
Medications
Rarely, radiation therapy
Immunodeficiency disorders may result from almost any prolonged serious disorder. For example, diabetes can result in an immunodeficiency disorder because white blood cells do not function well when the blood sugar level is high. Human immunodeficiency virus (HIV) infection may result in a secondary immunodeficiency disorder.
Many types of cancer can cause an immunodeficiency disorder. For example, any cancer that affects the bone marrow (such as leukemia or lymphoma) can prevent the bone marrow from producing normal white blood cells (B cells and T cells), which are part of the immune system.
Undernutrition—whether of all nutrients or only one—can impair the immune system. When undernutrition causes a significant decrease in weight, the immune system is often impaired.
Secondary immunodeficiency disorders also occur in older adults and people who are hospitalized.
Disorders That Can Cause Immunodeficiency
Type | Examples |
|---|---|
Blood | |
Cancer | Many types of cancers |
Chromosomal | |
Infectious | Chickenpox (varicella) Human immunodeficiency virus (HIV) infection Some bacterial infections |
Hormonal | |
Kidney | |
Liver | |
Musculoskeletal | Systemic lupus erythematosus (lupus) |
Spleen | Removal of spleen |
Other |
Immunosuppressants are medications used to intentionally suppress the activity of the immune system. For example, some are used to prevent rejection of a transplanted organ or tissue (see table Medications Used to Prevent Transplant Rejection). They may be given to people with an autoimmune disorder to suppress the body's attack against its own tissues.
Corticosteroids, a type of immunosuppressant, are used to suppress inflammation due to various disorders, such as rheumatoid arthritis. However, immunosuppressants also suppress the body’s ability to fight infections and perhaps to destroy cancer cells.
Chemotherapy and radiation therapy can also suppress the immune system, sometimes leading to immunodeficiency disorders.
Some Medications That Can Cause Immunodeficiency
Type | Examples |
|---|---|
Antiseizure medications | Valproate |
Chemotherapy agents | |
Corticosteroids | |
Immunosuppressants (medications that suppress the immune system) | |
Other medications such as laboratory-produced antibodies that target and suppress specific parts of the immune system |
Immunodeficiency in older adults
As people age, the immune system becomes less effective in several ways (see Effects of Aging on the Immune System). For example, as people age, they produce fewer T cells. T cells help the body recognize and fight foreign or abnormal cells.
Undernutrition, which is common among older adults, impairs the immune system. Undernutrition is usually thought of as a deficiency of calories, but it may also be a deficiency of one or more essential nutrients. Two nutrients that are particularly important to immunity—calcium and zinc—may be deficient in older adults. Calcium deficiency becomes more common among older adults, partly because as people age, the intestine becomes less able to absorb calcium. Also, older adults may not get enough calcium in their diet. Zinc deficiency is very common among older adults who are institutionalized or homebound.
Certain disorders (such as diabetes and chronic kidney disease), which are more common among older adults, and certain therapies (such as immunosuppressants) that older adults are more likely to use can also impair the immune system.
Symptoms of Immunodeficiency Disorders
People with an immunodeficiency disorder tend to have one infection after another. Usually, respiratory infections (such as sinus and lung infections) develop first and recur often. Most people eventually develop severe bacterial infections that persist, recur, or lead to complications. For example, sore throats and head colds may progress to pneumonia. However, having many colds does not necessarily suggest an immunodeficiency disorder. For example, a more likely cause of frequent infections in children is repeated exposure to infection at day care or school.
Infections of the mouth, eyes, and digestive tract are common. Thrush, a fungal infection of the mouth, may be an early sign of an immunodeficiency disorder. Sores may form in the mouth. People may have chronic gum disease (gingivitis) and frequent ear and skin infections. Bacterial infections (for example, with staphylococci) may cause pus-filled sores to form (pyoderma). People with certain immunodeficiency disorders may have many large, noticeable warts (caused by viruses).
Many people have fevers and chills and lose their appetite and/or weight.
Abdominal pain may develop, possibly because the liver or spleen is enlarged.
Infants or young children may have chronic diarrhea and may not grow and develop as expected (called failure to thrive). Children who develop symptoms in early childhood are likely to have a more severe immunodeficiency than those whose symptoms develop later.
Other symptoms vary depending on the severity and duration of the infections.
Primary immunodeficiencies may occur as part of a syndrome with other symptoms. These other symptoms are often more easily recognized than those of the immunodeficiency. For example, doctors may recognize DiGeorge syndrome because affected infants have low-set ears, a small jawbone that recedes, and wide-set eyes.
Although people with an immunodeficiency may have decreased ability to fight bacteria and other "foreign" substances, they can develop an immune response against their own tissues and develop symptoms of an autoimmune disorder.
Diagnosis of Immunodeficiency Disorders
Blood tests
Skin tests
A biopsy
Sometimes genetic testing
Doctors must first suspect that an immunodeficiency exists. Then they do tests to identify the specific immune system abnormality.
Doctors suspect immunodeficiency when one or more of the following occur:
A person has many recurrent infections (typically sinusitis, bronchitis, middle ear infections, or pneumonia).
Infections are severe or unusual.
A severe infection is caused by an organism that normally does not cause severe infection (such as Pneumocystis, fungi, or cytomegalovirus).
Recurring infections do not respond to treatment.
Family members also have frequent and severe recurring infections.
History
To help identify the type of immunodeficiency disorder, doctors ask at what age the person began to have recurring or unusual infections or other characteristic symptoms. Different types of immunodeficiency disorders are more likely depending on the age at which infections starts, as in the following:
Younger than 6 months: Usually an abnormality in T cells
Age 6 to 12 months: Possibly a problem with both B cells and T cells or with B cells
Older than 12 months: Usually an abnormality in B cells and antibody production
The type of infection may also help doctors identify the type of immunodeficiency disorder. For example, knowing which organ (ear, lungs, brain, or bladder) is affected, what the infecting organism is (bacteria, fungus, or virus), and what the organism's species is can help.
Doctors ask the person about risk factors, such as diabetes, use of certain medications, exposure to toxic substances such as certain pesticides or benzene, and the possibility of having close relatives with immunodeficiency disorders (family history). The person may also be asked about past and current sexual activity, use of intravenous drugs, and previous blood transfusions to determine whether HIV infection could be the cause.
Physical examination
Results of a physical examination may suggest immunodeficiency and sometimes the type of immunodeficiency disorder. For example, doctors suspect certain types of immunodeficiency disorders when the following are found:
The spleen is enlarged.
There are problems with the lymph nodes and tonsils.
In some types of immunodeficiency disorders, the lymph nodes are extremely small. In some other types, lymph nodes and tonsils are swollen and tender.
Tests
Laboratory tests are needed to confirm the diagnosis of immunodeficiency and to identify the type of immunodeficiency disorder.
Blood tests, including a complete blood count (CBC), are done. CBC can detect abnormalities in blood cells that are characteristic of specific immunodeficiency disorders. A blood sample is taken and analyzed to determine the total number of white blood cells and the percentages of each main type of white blood cell. The white blood cells are examined under a microscope for abnormalities. Doctors also determine immunoglobulin levels and the levels of certain specific antibodies produced after the person is given vaccines. If any results are abnormal, additional tests are usually done.
Skin tests may be done if the immunodeficiency is thought to be due to a T-cell abnormality. The skin test resembles the tuberculin skin test, which is used to screen for tuberculosis. Small amounts of proteins from common infectious organisms such as yeast are injected under the skin. If a reaction (redness, warmth, and swelling) occurs within 48 hours, the T cells are functioning normally. No reaction could suggest a T-cell abnormality. To confirm a T-cell abnormality, doctors do additional blood tests to determine the number of T cells and to evaluate T-cell function.
A biopsy may be done to help doctors identify which specific immunodeficiency disorder is causing the symptoms. For the biopsy, doctors take a sample of tissue from the lymph nodes and/or bone marrow. The sample is tested to determine whether certain immune cells are present.
Genetic testing may be done if doctors suspect a problem with the immune system. The gene mutation or mutations that cause many immunodeficiency disorders have been identified. Thus, genetic testing can sometimes help identify the specific immunodeficiency disorder. If a person has a genetic cause of immunodeficiency, some of their family members also may have the disorder or be carriers of the abnormal gene. Thus, doctors often recommend that close family members be evaluated, sometimes including genetic testing.
Screening for Immunodeficiency Disorders
Genetic testing, usually blood tests, may also be done in people whose families are known to carry a gene for a hereditary immunodeficiency disorder. These people may wish to be tested to learn whether they carry the gene for the disorder and what their chances of having an affected child are. Talking with a genetic counselor before testing is helpful.
Several immunodeficiency disorders, such as X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiency, and chronic granulomatous disease, can be detected in a fetus by testing a sample of the fluid around the fetus (amniotic fluid) or the fetus’s blood (prenatal testing). Such testing may be recommended for people with a family history of an immunodeficiency disorder when the mutation has been identified in the family.
Newborns are screened with a blood test that determines whether they have abnormal T cells or too few T cells—called the T-cell receptor excision circle (TREC) test. This test can identify some cellular immune deficiencies, such as severe combined immunodeficiency. Identifying infants with severe combined immunodeficiency early can help prevent their death at a young age. TREC testing of all newborns is now required in the United States.
Treatment of Immunodeficiency Disorders
General measures and certain vaccines to prevent infections
Antibiotics and antivirals when needed
Sometimes immune globulin
Sometimes stem cell transplantation
Treatment of immunodeficiency disorders usually involves preventing infections, treating infections when they occur, and replacing parts of the immune system that are missing when possible.
With appropriate treatment, many people with an immunodeficiency disorder have a normal life span. However, some require intensive and frequent treatments throughout life. Others, such as those with severe combined immunodeficiency, die during infancy unless they are given a stem cell transplant.
Preventing infections
Strategies for preventing and treating infections depend on the type of immunodeficiency disorder. For example, people who have an immunodeficiency disorder due to a deficiency of antibodies are at risk of bacterial infections. The following can help reduce the risk:
Practicing good personal hygiene (including conscientious dental care)
Not eating undercooked food
Not drinking water that may be contaminated
Avoiding contact with people who have infections
Being treated periodically with immune globulin (antibodies obtained from the blood of people with a normal immune system) given intravenously or under the skin
Vaccines are given if the specific immunodeficiency disorder does not affect antibody production. Vaccines are given to stimulate the body to produce antibodies that recognize and attack specific bacteria or viruses. If the person's immune system cannot make antibodies, giving a vaccine does not result in the production of antibodies and can even result in illness. For example, if a disorder does not affect production of antibodies, people with that disorder are given the influenza vaccine once a year. Doctors may also give this vaccine to the person's immediate family members and to people who have close contact with the person.
Generally, vaccines that contain live but weakened organisms (viruses or bacteria) are not given to people who have a B-cell or T-cell abnormality because these vaccines may cause an infection in such people. These vaccines include rotavirus vaccines, measles-mumps-rubella vaccine, chickenpox (varicella) vaccine, one type of varicella-zoster (shingles) vaccine, bacille Calmette-Guérin (BCG) vaccine, influenza vaccine given as a nasal spray, and oral poliovirus vaccine. The oral poliovirus vaccine is no longer used in the United States but is used in some other parts of the world.
Treating infections
Antibiotics are given as soon as a fever or another sign of an infection develops and often before surgical and dental procedures, which may introduce bacteria into the bloodstream. If a disorder (such as severe combined immunodeficiency) increases the risk of developing serious infections or particular infections, people may be given antibiotics long-term to prevent these infections.
Replacing missing parts of the immune system
Immune globulin can effectively replace missing antibodies (immunoglobulins) in people with an immunodeficiency that affects antibody production by B cells. Immune globulin may be injected into a vein (intravenously) once a month or under the skin (subcutaneously) once a week or once a month. Subcutaneous immune globulin can be given at home, often by the person with the disorder.
Stem cell transplantation can correct some immunodeficiency disorders, particularly severe combined immunodeficiency. Stem cells may be obtained from bone marrow or blood (including umbilical cord blood). Stem cell transplantation, which is available at some major medical centers, is usually reserved for severe disorders.
Transplantation of thymus tissue is sometimes helpful in treating some immunodeficiency disorders.
Gene therapy is an intervention with the potential to cure genetic disease. In gene therapy, a normal gene is inserted into someone's cells to correct a genetic abnormality causing a disorder. Gene therapy has been used successfully in various primary immunodeficiency disorders such as severe combined immunodeficiency, chronic granulomatous disease, , and others. Although there are various limitations and obstacles with the procedure, gene therapy provides promise for potential cures in the future.
Prevention of Immunodeficiency Disorders
Some of the disorders that can cause secondary immunodeficiency can be prevented and/or treated, thus helping prevent immunodeficiency from developing. The following are examples:
HIV infection: Measures to prevent HIV infection such as following safe sex guidelines and not sharing needles to inject drugs can reduce the spread of this infection. Also, antiretroviral medications can usually treat HIV infection effectively.
Cancer: Successful treatment can restore the function of the immune system unless people need to continue taking immunosuppressants.
Diabetes: Good control of blood sugar levels can help white blood cells function better and thus prevent infections.
More Information
The following English-language resource may be useful. Please note that The Manual is not responsible for the content of this resource.
Immune Deficiency Foundation: Comprehensive information on primary immunodeficiencies, from diagnosis and treatment to improving the quality of life for people affected
