There are many types of IDS, most of which are inherited or primary immunodeficiencies. Secondary immunodeficiencies are caused by an underlying disease or outside agent, such as HIV * or chemotherapy * .
B-cells or B lymphocytes are the antibody-producing cells of the humoral or antibody-mediated immune response. Bone marrow * stem cells develop into precursor B lymphocytes, which mature into B-cells. Each B-cell produces a specific antibody that recognizes and binds to a specific foreign antigen * , such as a bacterium or virus. When a B-cell encounters its antigen, it is stimulated to become a plasma cell and produces large amounts of antibodies that recognize that antigen.
Antibodies are protein molecules called immunoglobulins (Igs). There are five major classes of Igs:
Igs consist of four chains of amino acids * : two longer heavy chains and two shorter light chains that together form a Y-shaped protein. Each arm of the Y forms a binding site for the antibody's specific antigen.
T cells or T lymphocytes are part of the cellular or cell-mediated immune response:
Most IDS result from a failure in either the maturation of B-cells or the ability of B-cells to switch from one type of Ig production to another. With some types of IDS, the cellular immune system * retains its functions. However, B-cells are dependent on T-cells for producing antibodies; thus, some Ig deficiencies result from impaired T-cell function.
Primary IDS are caused by genetic * defects that are inherited as either X-linked or autosomal recessive traits. Recessive traits are usually only apparent in the absence of a normal copy of a gene. Because males have only one X chromosome, inherited from their mothers, genes for recessive disorders that are located on the X chromosome (X-linked) usually cause disease only in males. Females have two X chromosomes and are unlikely to inherit two X-linked defective genes * , although they can pass a defective gene on to their offspring. Autosomal recessive IDS are caused by defective genes on chromosomes other than the X chromosome. Autosomal recessive IDS affect both males and females, but tend to be less common than X-linked IDS.
There are many different types of primary IDS, involving many different genes. Some cause deficiencies in all types of Ig molecules and some affect only one or a few types:
Infants are born with their mothers’ antibodies circulating in their bloodstream. They begin producing their own antibodies by six months of age. Infants with transient * hypogammaglobulinemia have low antibody levels until they reach a year to three years of age. This condition is more common in premature infants and is believed to be due to the delayed development of T-helper cells. It is not inherited.
Primary IDS are much more common than was previously thought. They are the most common type of immunodeficiency disorder, accounting for about 50 percent of all primary immunodeficiencies.
Among selective IgG deficiencies, IgG2 deficiency is the most common in children and IgG3 deficiency is the most common in adults. IgG4 deficiency usually occurs in conjunction with IgG2 deficiency; however, IgG4 is not normally detectable until the age of 10. IgG1 deficiency is very rare. Selective IgA deficiency is one of the most common IDS, especially among Caucasians, affecting as many as 1 in 500 people. However, many people are unaware of their IgA deficiency.
IDS usually cause recurrent, severe, or chronic * infections—especially respiratory and gastrointestinal infections—from childhood on. The infections can spread to various organs.
Other symptoms of IDS may include the following:
Symptoms of CVID vary from mild to severe. The majority of CVID cases are not diagnosed until early adulthood. In about 20 percent of cases, the first symptom is a very low level of blood platelets * or severe anemia * due to antibodies destroying the body's own blood cells.
Infections due to HIM and selective IgG subclass deficiencies usually begin in the first or second year of life. Failure to produce specific antibodies in response to certain childhood vaccines * is a common symptom of an IgG subclass deficiency.
It is estimated that between 25 and 50 percent of people with selective IgA deficiency develop symptoms over a 20-year period. About one-half of people with known selective IgA deficiency are susceptible to infections and 25 to 33 percent have autoimmune diseases.
IDS are usually diagnosed by measuring the levels of the various Igs in the blood. If family members have IDS and the gene mutation is known, prenatal * diagnosis is possible. Other family members can also be tested to determine whether they carry the defective gene.
Boys with XLA usually have very small or absent tonsils and lymph nodes, because these tissues are made up of B-lymphocytes, and B-cells are generally absent from the blood. XLA can be confirmed by the absence of BTK protein in white blood cells or platelets or by detecting a BTK mutation in the DNA * . Although there are many different BTK mutations, family members usually share the same one. Any male newborn with a brother or maternal uncle or cousin with XLA should be immediately tested for the percentage of B-cells in his blood, so he can be treated before he becomes ill.
Patients with CVID usually have very low or undetectable levels of antibodies against polio, measles * , diphtheria * , and tetanus * despite immunizations. Sometimes the degree of immunoglobulin deficiency is determined by measuring antibody levels following vaccinations. The number and function of T-lymphocytes in the blood may also be measured. Tissue cultures * can determine whether B-cells make antibodies and whether T-cells are functioning properly.
XHIM is diagnosed by the absence of a protein called CD40 ligand on the surfaces of activated T-cells and identification of a mutation in the CD40 ligand gene. Autosomal recessive forms of HIM have similar symptoms to XHIM but may occur in females or the CD40 ligand is normal. HIM diagnosis can be confirmed by mutation analysis of the genes involved.
Most primary IDS can be treated effectively. Antibiotics * are used to prevent and treat infections. Severe IDS are treated with immunoglobulin replacement therapy. Other treatments are as follows:
Maximizing resistance to infection includes the following:
Good hygiene for patients and their families is essential for reducing the risk of infection:
Patients with IDS should not be given any live-virus vaccines such as live polio or measles, mumps * , or rubella (MMR).
Etzioni, Amos, and Hans D. Ochs, eds. Primary Immunodeficiency Disorders: A Historic and Scientific Perspective. Waltham, MA: Academic Press, 2014.
Immune Deficiency Foundation. Patient & Family Handbook for Primary Immunodeficiency Diseases, 5th ed. Towson, MD: Immune Deficiency Foundation, 2013. http://primaryimmune.org/wpcontent/uploads/2013/06/IDF_Patient_Family_Handbook_5th_Edition.pdf (accessed July 20, 2015).
Genetics Home Reference. “Common Variable Immune Deficiency.” U.S. National Library of Medicine. 10_p871-962_ChI_V2_JETcombined.10.6edit.docxhttp://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency (accessed July 20, 2015).
Immune Disease.com . “Types of PI.” http://www.immunedisease.com/about-pi/types-of-pi/common-variable-immunodeficiency-cvid.html (accessed July 20, 2015).
PrimaryImmune.org . “IgG Subclass Deficiency.” http://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/igg-subclass-deficiency (accessed September 21, 2015).
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* immunoglobulins (im-muneo-GLOB-u-linz) are types of antibodies.
* antibodies (AN-tih-bah-deez) are protein molecules produced by the body's immune system to help fight specific infections caused by microorganisms, such as bacteria and viruses.
* HIV, or human immunodeficiency virus (HYOO-mun ih-myoo-no-dih-FIH-shen-see), is the virus that causes AIDS (acquired immunodeficiency syndrome).
* chemotherapy (KEE-mo-THER-a-pee) is the treatment of cancer with powerful drugs that kill cancer cells. * bone marrow is the soft tissue inside bones where blood cells are made.
* antigen (AN-tih-jen) is a substance that is recognized as a threat by the body's immune system, which triggers the formation of specific antibodies against the substance.
* bile is a greenish-brown fluid manufactured in the liver that is essential for digesting food. Bile is stored in the gallbladder, which contracts and discharges bile into the intestine to aid digestion of fats after a person eats.
* mucus (MYOO-kus) is a thick, slippery substance that lines the insides of many body parts.
* amino acids (a-MEE-no acids) are the chief building blocks of proteins. In humans, certain amino acids are required to sustain life.
* immune system (im-YOON SIS-tem) is the system of the body composed of specialized cells and the substances they produce that helps protect the body against disease-causing germs.
* genetic (juh-NEH-tik) refers to heredity and the ways in which genes control the development and maintenance of organisms.
* chromosome (KRO-mo-zom) is a unit or strand of DNA, the chemical substance that contains the genetic code to build and maintain a living being. Humans have 23 pairs of chromosomes, for a total of 46.
* genes (JEENS) are chemical structures composed of deoxyribonucleic acid (DNA) that help determine a person's body structure and physical characteristics. Inherited from a person's parents, genes are contained in the chromosomes found in the body's cells.
* mutation (myoo-TAY-shun) is a change in an organism's gene or genes.
* syndrome is a group or pattern of symptoms or signs that occur together.
* transient (TRAN-shent) means brief, or producing effects for a short period of time.
* chronic (KRAH-nik) means lasting a long time or recurring frequently.
* nutrients are the components of food (protein, carbohydrate, fat, vitamins, and minerals) needed for growth and maintenance of the body.
* lymph nodes (LIMF) are small, bean-shaped masses of tissue containing immune system cells that fight harmful microorganisms. Lymph nodes may swell during infections.
* spleen is an organ in the upper left part of the abdomen that stores and filters blood. As part of the immune system, the spleen also plays a role in fighting infection.
* autoimmune diseases (aw-tohih-MYOON) are diseases in which the body's immune system attacks some of the body's own normal tissues and cells.
* arthritis (ar-THRY-tis) refers to any of several disorders characterized by inflammation of the joints.
* failure to thrive is a condition in which an infant fails to gain weight and grow at the expected rate.
* platelets (PLATE-lets) are tiny disk-shaped particles within the blood that play an important role in clotting.
* anemia (uh-NEE-me-uh) is a blood condition in which there is a decreased hemoglobin in the blood and, usually, fewer than normal numbers of red blood cells.
* vaccines (vak-SEENS) are preparations of killed or weakened germs, or a part of a germ or product it produces, given to prevent or lessen the severity of the disease that can result if a person is exposed to the germ itself. Use of vaccines for this purpose is called immunization.
* prenatal (pre-NAY-tal) means existing or occurring before birth, with reference to the fetus.
* DNA, or deoxyribonucleic acid (dee-OX-see-ry-bo-nyoo-klay-ik AH-sid), is the specialized chemical substance that contains the genetic code necessary to build and maintain the structures and functions of living organisms.
* measles (ME-zuls) is a viral respiratory infection that is best known for the rash of large, flat, red blotches that appear on the arms, face, neck, and body.
* diphtheria (dif-THEER-e-uh) is an infection of the lining of the upper respiratory tract (the nose and throat). It is a disease that can cause breathing difficulty and other complications, including death.
* tetanus (TET-nus) is a serious bacterial infection that affects the body's central nervous system.
* bone marrow is the soft tissue inside bones where blood cells are made.
* cultures (KUL-churz) are tests in which a sample of fluid or tissue from the body is placed in a dish containing material that supports the growth of certain organisms. Typically, within days, the organisms will grow and can be identified
* antibiotics (an-tie-by-AH-tiks) are drugs that kill or slow the growth of bacteria.
* transplants (TRANS-plantz) are organs or tissues from another body used to replace a poorly functioning organ or tissue.
* gamma globulin (GAH-muh GLAH-byoo-lin) is a type of protein in the blood that contains the antibodies produced by the cells of the body's immune system that help defend the body against infection-causing germs, such as bacteria and viruses.
* liver is a large organ located beneath the ribs on the right side of the body. The liver performs numerous digestive and chemical functions essential for health.
* mumps is a contagious viral infection that causes inflammation and swelling in the glands of the mouth that produce saliva.