Overview of Immunodeficiency Disorders

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.

Primary immunodeficiency disorders are classified by which part of the immune system Overview of the Immune System The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites... read more is affected:

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.

These disorders can result from

Immunodeficiency disorders may result from almost any prolonged serious disorder. For example, diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more 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 Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and is treated with antiretroviral medications. If untreated, it can cause... read more results in acquired immunodeficiency syndrome (AIDS), the most common severe acquired immunodeficiency disorder.

Many types of cancer can cause an immunodeficiency disorder. For example, any cancer that affects the bone marrow (such as leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more or lymphoma 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 ) can prevent the bone marrow from producing normal white blood cells (B cells and T cells), which are part of the immune system.

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 —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.

Immunosuppressants are drugs 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 ). 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 , 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.

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 , 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, alcohol use disorder, and use of diuretics. People lose their appetite and hair and may feel sluggish and lose their sense of taste... read more is very common among older people who are institutionalized or homebound.

Certain disorders (such as diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more and chronic kidney disease Chronic Kidney Disease Chronic kidney disease is a slowly progressive (months to years) decline in the kidneys’ ability to filter metabolic waste products from the blood. Major causes are diabetes and high blood pressure... read more ), which are more common among older people, and certain therapies (such as immunosuppressants), which older people are more likely to use, can also impair the immune system.

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:

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 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 Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and is treated with antiretroviral medications. If untreated, it can cause... read more could be the cause.

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:

In some types of immunodeficiency disorders, the lymph nodes are extremely small. In some other types, lymph nodes and tonsils are swollen and tender.

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. 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.

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:

Vaccines Overview of Immunization Immunization (vaccination) helps the body defend itself against diseases caused by certain bacteria or viruses. Immunity (the ability of the body to defend itself against diseases caused by... 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.

Antibiotics Overview of Antibiotics Antibiotics are drugs used to treat bacterial infections. They are not effective against viral infections and most other infections. Antibiotics either kill bacteria 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.

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.

Gene therapy, along with transplantation, 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 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 , 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 , adenosine deaminase deficiency Severe Combined Immunodeficiency (SCID) , and others. Although there are various limitations and obstacles with the procedure, gene therapy provides promise for potential cures in the future.