Primary Immunedeficiency Disease: Introduction

When part of the immune system is either absent or not functioning properly, it can result in an immune deficiency disease. When the cause of this deficiency is hereditary or genetic, it is called a primary immunodeficiency disease (PIDD). Researchers have identified more than 150* different kinds of PIDD.

The immune system is composed of white blood cells. These cells are made in the bone marrow and travel through the bloodstream and lymph nodes. They protect and defend against attacks by "foreign" invaders such as germs, bacteria and fungi.

In the most common PIDDs, different forms of these cells are missing. This creates a pattern of repeated infections, severe infections and/or infections that are unusually hard to cure. These infections may attack the skin, respiratory system, the ears, the brain or spinal cord, or in the urinary or gastrointestinal tracts.

In some instances, PIDD targets specific and/or multiple organs, glands, cells and tissues. For example, heart defects are present in some PIDDs. Other PIDDs alter facial features, some stunt normal growth and still others are connected to autoimmune disorders such as rheumatoid arthritis.

Chronic Granulomatous Disease (CGD) »

Common Variable Immunodeficiency (CVID) »

DiGeorge Syndrome (DGS) »

Selective IgA Deficiency »

Severe Combined Immunodeficiency (SCID) »

X-Linked Agammaglobulinemia (XLA) »

Chronic Granulomatous Disease (CGD)
CGD Overview
Chronic Granulomatous Disease (CGD) is an inherited primary immunodeficiency disease (PIDD) which increases the body’s susceptibility to infections caused by certain bacteria and fungi. Granulomas are masses of immune cells that form at sites of infection or inflammation.

People with CGD are unable to fight off common germs and get very sick from infections that would be mild in healthy people. Children with CGD are often healthy at birth. The most common form of CGD is genetically inherited in an X-linked manner. For this reason. but develop severe infections in infancy or early childhood. CGD may involve any organ system or tissue of the body. Diagnosis The timing of diagnosing CGD is often dependent upon when an infant or child begins having recurrent bacterial or fungal infections associated with the disease. People with CGD can be generally healthy until they become infected with one of these germs. Pneumonia caused by a fungus such as Aspergillus is a red flag for CGD and often results in testing. meaning it only affects boys. The immune system requires hydrogen peroxide to fight specific kinds of bacteria and fungi. liver or brain). the rest of the immune system is normal. This is because the presence of CGD makes it difficult for cells called neutrophils to produce hydrogen peroxide. Aside from the defective neutrophil function in CGD. CGD Symptoms & Diagnosis Symptoms People with CGD can easily fight off some infections. . symptoms of recurrent bacterial or fungal infections may be sporadic. but not those that need the body’s natural ability to produce hydrogen peroxide to control disease. but infections are usually found in the: • Skin • Lungs • Lymph nodes • Liver • Bones • Occasionally the brain Wounds may also have trouble healing and an inflammatory condition known as granuloma may develop. The severity of this infection can lead to prolonged hospitalizations for treatment. There are also autosomal recessive forms of CGD that affect both sexes. These severe infections can include skin or bone infections and abscesses in internal organs (such as the lungs.

CGD Treatment & Management The best treatment plan for CGD is to prevent infections from occurring. bronchi and lungs. nose. It is one of the most common forms of primary immunodeficiency disease (PIDD). CVID can be associated with autoimmune disorders that affect other blood cells causing low numbers of white cells or platelets. sinuses. These include: • Pneumonia • Sinusitis . These greatly reduce the chances of infection. As with other antibody deficiencies. Both males and females are affected. People with CVID are also at an increased risk for certain cancers. arthritis and other conditions.The most accurate test to confirm CGD is made by measuring the amount of hydrogen peroxide produced by the body’s cells. CVID Symptoms & Diagnosis Symptoms CVID can be diagnosed anytime from childhood through adulthood. resulting in recurrent and often severe infections. and the severity of symptoms varies from one person with the disease to another. Bone marrow transplant is another treatment option for some people with severe symptoms of CGD. Special preventative antibiotics are a mainstay of treatment for CGD. The exact cause and genetic inheritance pattern of CVID is unknown in most cases. Common Variable Immunodeficiency (CVID) CVID Overview Common Variable Immunodeficiency (CVID) is an antibody deficiency that leaves the immune system unable to defend against bacteria and viruses. the most common types of recurrent infections involve the ears. anemia.

DiGeorge Syndrome (DGS) DGS Overview DiGeorge Syndrome (DGS) is a primary immunodeficiency disease (PIDD) associated with susceptibility to infections due to poor T cell production and function. which can complicate treatment. Children with DGS differ in the organs and tissues affected. Diagnosis CVID may be suspected in children or adults with a history of recurrent infections involving the lungs. . abnormal gland development or defects in organs such as the heart. Still. Antibiotics are used to treat most infections that result from CVID though patients may need treatment for a longer duration than a healthy individual. An accurate diagnosis can be made through screening tests that measure immunoglobulin levels or the number of B cells in the blood. recurrent infections tend to decrease in late childhood and adulthood. While DGS is a lifelong condition. ears or sinuses. DGS is caused by abnormal cell and tissue development during fetal growth.• Ear infections • Gastrointestinal infections Recurrent pneumonia and chronic infections in the lungs can lead to lung damage called bronchiectasis. it mostly affects infants and children. IRT treatments must be given regularly and are life-long. as well as in the severity of the disease. Depending on the severity of the syndrome. In addition to possible immune system problems. approximately one-third of affected adults will have mild recurrent infections. this abnormal development can result in altered facial characteristics. bronchi. CVID Treatment & Management CVID is treated with immunoglobulin replacement therapy (IRT). which most often relieves symptoms.

immunology. mild T cell problems can often be managed with antibiotics and close follow-up. cases of DGS in which T cell development is severely affected have been successfully treated with bone marrow or thymus transplant. genetics and speech therapy. For instance.low set ears. a short philtrum (the vertical groove on the upper lip). Children with DGS benefit from a multi-specialty approach to treatment. Nasal-sounding speech can occur when a cleft palate is involved. Based on which organs are affected by the syndrome. On the other extreme. other symptoms may include: • Frequent infections • Low calcium levels • Heart defects Diagnosis DGS is often diagnosed at birth or in infancy based on clinical observation of multiple symptoms with various organs. Some people with DGS are susceptible to infections due to poor T cell production and function.Most cases result from a deletion of chromosome 22q11.2 (the DGS chromosome region). treatment plans for DGS must be personalized. learning difficulties or certain psychiatric disorders are also common. Severe problems involving the heart or facial features may require corrective surgery. . DGS Symptoms & Diagnosis Symptoms Certain facial features are often seen with DGS . Short stature. notably 10p13. heavy eyelids and/or a small mouth. T cells are white blood cells that are important for protection against infections. underdeveloped chin. since this disease can be associated with a spectrum of disorders that fall under varying different medical specialties including ENT. cardiology. DGS Treatment & Management As the organs and tissues involved and the severity of the abnormalities vary. A genetic test is used to confirm the diagnosis. a bulbous nose tip. A small number of cases of DGS have defects in another chromosome.

airways and digestive tract. Unlike many other immunoglobulin deficiencies. Diagnosis requires blood screening to show an IgA deficiency but normal levels of other immunoglobulins. A common problem in IgA deficiency is susceptibility to infections. Also. A second major problem in IgA deficiency is increased occurrence of autoimmune diseases. Selective IgA Deficiency Treatment & Management The underlying cause for Selective IgA Deficiency is unknown and there is currently no way to replace IgA in the body. Although individuals with Selective IgA Deficiency do not produce IgA. People with this disorder have absent levels of a blood protein called immunoglobulin A (IgA). many people with Selective IgA Deficiency also have allergies or asthma. in which the immune system attacks itself. IgA protects against infections of the mucous membranes lining the mouth. Selective IgA Deficiency Symptoms & Diagnosis The most common symptom of Selective IgA Deficiency is susceptibility to infections including: • Pneumonia • Sinusitis • Ear infections • Chronic diarrhea caused by gastrointestinal infections IgA deficiency may also cause autoimmune disease. they do produce all the other kinds of immunoglobulin. . This is why many people with IgA deficiency appear healthy or only have mild reoccurring illness such as gastrointestinal infections. Common examples of these diseases are rheumatoid arthritis and lupus.Selective IgA Deficiency Selective IgA Deficiency Overview Selective IgA Deficiency is the most common primary immunodeficiency disease (PIDD). the condition is not treated with immunoglobulin replacement therapy.

preventative antibiotics may be used to help diminish the frequency of infections. It is considered to be the most serious primary immunodeficiency disease (PIDD). Women may carry the condition. affecting only males. it may require several hospitalizations before SCID is diagnosed. but they also inherit a normal X chromosome. B cells and NK cells can also be affected. although all of these symptoms may not be present. Severe Combined Immunodeficiency (SCID) SCID Overview Severe Combined Immunodeficiency (SCID) is a rare. These cells play important roles in helping the immune system battle bacteria. There are several forms of SCID. Infants with SCID often suffer from recurrent.In cases where recurrent infections are a problem. . inherited condition resulting in a weak immune system that is unable to fight off even mild infections. on the other hand. SCID is caused by a genetic defect that affects the function of T cells. rashes that look like eczema. Often. Individuals with IgA deficiency often require a longer course of antibiotics for infections to clear up. Depending on the type of SCID. Other forms of SCID are caused by a deficiency of the enzyme adenosine deaminase (ADA) and a variety of other genetic defects. SCID is associated with recurrent viral infections and causes several hospitalizations before it is discovered. Men. viruses and fungi that cause infections. SCID Symptoms & Diagnosis Symptoms In addition to frequent and often very severe respiratory infections. other symptoms of SCID in infants include poor growth. have only one X chromosome. Symptoms of the disease are frequently first noticed very early in life. These infections are usually serious and may even be lifethreatening. chronic diarrhea and recurrent thrush in the mouth. severe respiratory infections. Still. The most common type is linked to a problem in a gene on the X chromosome.

One unusual infection that can be present with SCID early on is pneumocystis pneumonia. B cells are responsible for producing the antibodies that the immune system relies on to fight off infection. XLA is caused by a genetic mistake in a gene called Bruton's Tyrosine Kinase (BTK). which provides a new immune system to the patient. As with other PIDD. Staphylococcus and Haemophilus. SCID Treatment & Management The only cure currently and routinely available for SCID is bone marrow transplant. X-Linked Agammaglobulinemia (XLA) XLA Overview X-Linked Agammaglobulinemia (XLA) is an inherited immunodeficiency in which the body is unable to produce the antibodies needed to defend against bacteria and viruses. Treating the disease in the first months of life offers a very positive success rate in helping to combat SCID. Presence of this infection is a red flag for the need to evaluate the immune system for SCID. XLA Symptoms & Diagnosis . The most common bacteria causing infection in XLA are Streptococcus. A diagnosis of SCID can be made in utero. screening tests can measure blood lymphocytes levels. Other forms of combined immunodeficiency can occur that may not require bone marrow transplantation. prompt evaluation by an immunology specialist is crucial for early treatment. Learn about the IDF newborn screening initiative and view a United States map indicating where each state is in terms of newborn screening. which is especially helpful if there is a family history of immunodeficiency diseases. but not without complications. Frequently called Bruton's Agammaglobulinemia. Research on gene therapy for SCID is continuing and may one day be a good option. which prevents B cells from developing normally. Diagnosis Early detection of SCID is extremely important. If you think your child may have SCID. Gene therapy treatment of SCID has also been successful in clinical trials.

When affected by XLA. Diagnosis XLA can be detected through screening tests that measure immunoglobulin levels or the number of B cells in the blood. Immunoglobulin replacement therapy is a life-long and life-saving treatment that restores some of the missing antibodies. the infant cannot do this on his own. mumps or rubella. XLA Treatment & Management There is no cure for XLA. some people benefit from a daily course of oral antibiotics to prevent or treat infections. In addition. and then the infant needs to start producing antibodies on its own.Symptoms XLA often becomes apparent in infancy due to recurrent and severe bacterial infections including: • Ear infections • Sinusitis • Pneumonia • Diarrhea due to a parasite called Giardia When a baby is first born. Though rare. . Live viral vaccines. these vaccines can infect the recipient with the very disease they were intended to prevent. but the condition can be successfully treated. Most individuals with XLA who receive immunoglobulin on a regular basis can lead relatively normal lives. it is protected from infection by IgG antibodies that are passed through the placenta from the mother. measles. This maternal IgG only lasts for several months. such as those for polio. are not considered safe for people with XLA. This is true for most B and T cell immune defects. and becomes susceptible to these recurrent infections.

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