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Overview of Immunodeficiency Disorders

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Last full review/revision Apr 2021| Content last modified Apr 2021
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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 drug 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.

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 Overview of Lymphoma Lymphomas are cancers of lymphocytes, which reside in the lymphatic system and in blood-forming organs. Lymphomas are cancers of a specific type of white blood cells known as lymphocytes. These... read more Overview of Lymphoma or other cancers may develop.

There are two types of 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 Inheritance Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are made of a very long strand... read more . X-linked disorders occur more often in boys. About 60% of people with primary immunodeficiency disorders are male.

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.

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Secondary immunodeficiency disorders

These disorders can result from

  • Prolonged (chronic) and/or serious disorders such as diabetes or cancer

  • Drugs

  • Rarely, radiation therapy

Undernutrition Undernutrition Undernutrition is a deficiency of calories or of one or more essential nutrients. Undernutrition may develop because people cannot obtain or prepare food, have a disorder that makes eating or... read more Undernutrition —whether of all nutrients or only one—can impair the immune system. When undernutrition causes weight to decrease to less than 80% of recommended weight, the immune system is often impaired. A decrease to less than 70% usually results in severe impairment.

Secondary immunodeficiency disorders also occur in older people and people who are hospitalized.

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Immunosuppressants are drugs used to intentionally suppress the immune system. For example, some are used to prevent rejection of a transplanted organ or tissue (see table Drugs Used to Prevent Transplant Rejection Drugs Used to Prevent Transplant Rejection Transplantation is the removal of living, functioning cells, tissues, or organs from the body and then their transfer back into the same body or into a different body. The most common type of... read more ). They may be given to people with an autoimmune disorder to suppress the body's attack against its own tissues.

Corticosteroids Corticosteroids Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints.... read more 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.

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Immunodeficiency in older people

As people age, the immune system becomes less effective in several ways (see Effects of Aging on the Immune System Effects of Aging on the Immune System The immune system is the body's defense against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites (such... read more ). For example, as people age, they produce fewer T cells. T cells help the body recognize and fight foreign or abnormal cells.

Undernutrition Undernutrition Undernutrition is a deficiency of calories or of one or more essential nutrients. Undernutrition may develop because people cannot obtain or prepare food, have a disorder that makes eating or... read more Undernutrition , which is common among older people, 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 people. Calcium deficiency Hypocalcemia (Low Level of Calcium in the Blood) In hypocalcemia, the calcium level in blood is too low. A low calcium level may result from a problem with the parathyroid glands, as well as from diet, kidney disorders, or certain drugs. As... read more becomes more common among older people, partly because as people age, the intestine becomes less able to absorb calcium. Also, older people may not get enough calcium in their diet. Zinc deficiency Zinc Deficiency Zinc deficiency has many causes, including various disorders, alcoholism, and use of diuretics. People lose their appetite and hair and may feel sluggish and lose their sense of taste. Doctors... read more Zinc Deficiency is very common among older people who are institutionalized or homebound.

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 Pneumonia in Immunocompromised People Pneumonia is infection of the lungs. Pneumonia in people whose immune system is weakened or impaired (for example, by acquired immunodeficiency syndrome [AIDS], cancer, organ transplantation... read more . 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 Chronic Mucocutaneous Candidiasis Chronic mucocutaneous candidiasis, a hereditary immunodeficiency disorder, is persistent or recurring infection with Candida (a fungus) due to malfunction of T cells (lymphocytes). Chronic mucocutaneous... read more Chronic Mucocutaneous Candidiasis , 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 Gingivitis Gingivitis is mild form of periodontal disease characterized by inflammation of the gums (gingivae). Gingivitis results most often from inadequate brushing and flossing but may result from medical... read more 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 Failure to Thrive Failure to thrive is a delay in weight gain and physical growth that can lead to delays in development and maturation. Medical disorders and a lack of proper nutrition are causes of failure... read more ). Immunodeficiency may be more severe if symptoms develop in early childhood than if they 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 DiGeorge Syndrome DiGeorge syndrome is a congenital immunodeficiency disorder in which the thymus gland is absent or underdeveloped at birth. Children with DiGeorge syndrome are born with several abnormalities... read more 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 Autoimmune Disorders An autoimmune disorder is a malfunction of the body's immune system that causes the body to attack its own tissues. What triggers autoimmune disorders is not known. Symptoms vary depending on... read more .

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.

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.

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 drugs, exposure to toxic substances, 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 Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS). HIV is transmitted... read more Human Immunodeficiency Virus (HIV) Infection could be the cause.

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 Complete blood count Doctors select tests to help diagnose blood disorders based on the person's symptoms and the results of the physical examination. Sometimes a blood disorder causes no symptoms but is discovered... read more (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.

Screening

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 X-Linked Agammaglobulinemia X-linked agammaglobulinemia is a hereditary immunodeficiency disorder due to a mutation in a gene on the X (sex) chromosome. The disorder results in no B cells (a type of lymphocyte) and very... read more , Wiskott-Aldrich syndrome Wiskott-Aldrich Syndrome Wiskott-Aldrich syndrome is a hereditary immunodeficiency disorder characterized by abnormal antibody (immunoglobulin) production, T-cell (lymphocyte) malfunction, a low platelet count, and... read more , severe combined immunodeficiency Severe Combined Immunodeficiency (SCID) Severe combined immunodeficiency is a primary immunodeficiency disorder resulting in low levels of antibodies (immunoglobulins) and low or no T cells (lymphocytes). Most infants with severe... read more , and chronic granulomatous disease Chronic Granulomatous Disease (CGD) Chronic granulomatous disease is a hereditary immunodeficiency disorder in which phagocytes (a type of white blood cell) malfunction. People with chronic granulomatous disease have persistent... read more , 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 Procedures Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more ). Such testing may be recommended for people with a family history of an immunodeficiency disorder when the mutation has been identified in the family.

Some experts recommend screening all newborns 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 Severe Combined Immunodeficiency (SCID) Severe combined immunodeficiency is a primary immunodeficiency disorder resulting in low levels of antibodies (immunoglobulins) and low or no T cells (lymphocytes). Most infants with severe... read more . 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 many U.S. states.

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:

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 Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more .

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:

  • Being treated periodically with immune globulin (antibodies obtained from the blood of people with a normal immune system) given intravenously or under the skin

  • 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

Vaccines Overview of Immunization Immunization enables the body to better defend itself against diseases caused by certain bacteria or viruses. Immunity (the ability of the body to defend itself against diseases caused by certain... read more 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- 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 Overview of Antibiotics Antibiotics are drugs used to treat bacterial infections. They are ineffective against viral infections and most other infections. Antibiotics either kill microorganisms or stop them from reproducing... read more 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.

Antiviral drugs Antiviral drugs A virus is composed of nucleic acid, either DNA or RNA, surrounded by a protein coat. It requires a living cell in which to multiply. A viral infection can lead to a spectrum of symptoms from... read more are given at the first sign of infection if people have an immunodeficiency disorder that increases the risk of viral infections (such as immunodeficiency due to a T-cell abnormality). These drugs include oseltamivir or zanamivir for influenza and acyclovir for herpes or chickenpox.

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 Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more 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.

More Information

The following is an English-language resource that 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

Drugs Mentioned In This Article

Generic Name Select Brand Names
MEDROL
CYTOXAN (LYOPHILIZED)
Gammagard S/D
Mycophenolate
IMURAN
NEORAL, SANDIMMUNE
TAMIFLU
ACTEMRA
CAMPATH
LAMICTAL
HUMIRA
ENBREL
REMICADE
RAYOS
PROGRAF
ZOVIRAX
RITUXAN
DILANTIN
RAPAMUNE
ALKERAN
RELENZA
MYLERAN
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