Primary Immunodeficiency

We live in a world teeming with germs (Read about "Microorganisms") and we rely on our immune system (Read about "The Immune System") to protect us from them. But for some people, the immune system does not do its job because it is missing certain components. (Read about "Immune System Glossary") According to the National Institutes of Health (NIH), those people could have primary immunodeficiency disorder - or PI. A PI disease results when essential parts of the immune system, such as Immunoglobulin A (IgA), are missing or not working properly because of genetic defects. (Read about "Genetics") This can lead to frequent infections that are difficult, if not impossible, to fight.

Individuals with PI - many of them infants and children - get one infection after another. Ear, sinus, and other infections (Read about "Otitis Media" "Sinusitis & Rhinitis") may not improve with treatment as expected, but keep coming back or occurring with less common but severe infections, such as recurrent pneumonia. (Read about "Pneumonia") Besides being painful, frightening and frustrating, these constant infections can cause permanent damage to the ears or to the lungs. In the more severe forms of PI, germs that cause only mild infections in people with healthy immune systems may cause severe or life-threatening infections.

The National Institute of Child Health and Human Development (NICHD) says, although infections are the hallmark of PIs, they are not always the only health problem or even the main one. Some PIs are associated with other immune system disorders, such as anemia, arthritis or autoimmune diseases. (Read about "Anemia" "Arthritis & Rheumatic Diseases") Other PIs involve more than the immune system; some, for instance, are associated with symptoms involving the heart, digestive tract, or the nervous system. (Read about "Nervous System") Some PIs retard growth and increase the risk of cancer. (Read about "Cancer: What It Is")

PI diseases were once thought to be rare, mostly because only the more severe forms were recognized, according to NICHD. Today physicians realize that PIs are not uncommon. They are sometimes relatively mild, and they can occur in teenagers and adults as often as in infants and children.

Very serious inherited immunodeficiencies become apparent almost as soon as a baby is born. Many more are discovered during the baby's first year of life. (Read about "Child Development") Others - usually the milder forms - may not show up until people reach their twenties and thirties. There are even some inherited immune deficiencies that never produce symptoms, according to NICHD.

The exact number of persons with PI is not known. It is estimated by NICHD, that each year about 400 children are born in the United States with a serious PI. The number of Americans now living with a serious primary immunodeficiency is estimated to be between 25,000 and 50,000.

The National Primary Immunodeficiency Resource Center (NPI) estimates there are 100 different PI disorders. Some types are common; others are extremely rare. Similarly, some conditions are life threatening while others may cause few, if any, symptoms.

Here are a few examples from NICHD and NPI:

• Selective IgA (Immunoglobulin A) Deficiency: According to NIH, this is a common PI. Estimates range from one out of every 300 people, to one in 1,000. IgA Deficiency sometimes seems to run in families. Selective IgA Deficiency is characterized by a deficiency of immunoglobulins in body secretions and the mucous membranes lining the airways and digestive tract. IgA normally stands guard at the body entrances, intercepting bacteria, viruses, toxins and certain food components. The cause of IgA Deficiency is not known, and it may differ from one person to the next. In fact, NIH says some people with IgA Deficiency may not have symptoms. Others may experience recurring ear, sinus or lung infections. IgA Deficiency itself seldom causes serious trouble. However, people with IgA Deficiency are very likely to have any of a variety of other problems. They are especially prone to allergies, asthma (Read about "Allergies" "Asthma"), autoimmune diseases such as rheumatoid arthritis and diabetes (Read about "Rheumatoid Arthritis" "Diabetes"); diseases of the gastrointestinal tract, and neurologic diseases. (Read about "Digestive System" "Brain/Mental Health/Nervous System") Thus, anyone diagnosed with IgA Deficiency should have periodic check-ups to look for such possibilities.
• IgG Subclass Deficiency: NPI terms this a fairly common PI disorder. Immunoglobulin G (IgG) is the main immunoglobulin working in the blood and tissues, according to NICHD. IgG antibodies coat germs so that immune cells have an easier time of engulfing them. NPI lists recurring sinusitis, bronchitis and pneumonia (Read about "Sinusitis & Rhinitis" "COPD: Emphysema & Bronchitis" "Pneumonia") as most frequently observed in patients with IgG Subclass Deficiency. In this case, one or two of the four subclasses of IgG (IgG1, IgG2, IgG3 and IgG4) is deficient. Each IgG subclass plays a slightly different role. IgG1 and IgG3 antibodies are formed in response to certain proteins, including toxins produced by some bacteria and the proteins of some viruses. IgG2 antibodies target the capsules that shield certain bacteria. Antibodies of some IgG subclasses cooperate with the complement system; others do not. As a result of such differences, each type of subclass deficiency leaves a person vulnerable to specific types of infections.
• DiGeorge Syndrome (22q11.2 deletion syndrome): According to the National Center for Biotechnology Information (NCBI), this is a rare disorder that is present at birth. It is caused by missing material in chromosome 22. (Read about "Genetics") Several genes can end up missing. The symptoms of the condition vary by how much genetic information is missing. The symptoms of DiGeorge may be different for each child, depending on which organs are abnormally affected. The abnormalities can range from mild to severe. Symptoms include recurrent infections, heart defects (Read about "Congenital Heart Defects") and learning difficulties. Some children with DiGeorge have a distinctive look, with an underdeveloped chin, eyes that slant downward and misshapen ear lobes. Some children also have underdeveloped parathyroid glands. (Read about "Parathyroid Glands") The parathyroids, located in the neck next to the thyroid gland (Read about "Thyroid"), produce a hormone that helps to control levels of calcium (Read about "Calcium") in the blood; when calcium levels are not balanced, the child can develop convulsions. (Read about "Seizures") Many children with DiGeorge have a very small thymus (Read about the thymus in "Endocrine System") that is normal. In others, the thymus is missing altogether. The thymus produces T-cells, which play an important role in our immune response.
• Common Variable Immunodeficiency (CVID): CVID is the name given to a group of disorders characterized by low levels of gammaglobulins and too few IgA antibodies. NPI lists this as a relatively common PI deficiency affecting one in every 50,000 people. NPI says symptoms may vary, but most include recurrent infections, disorders of the joints, skin and gastrointestinal complaints. People with CVID may have normal numbers of B cells, but their B cells don't function properly. B cells play a major role in our immune response. Their T cells also show a variety of defects. Like most antibody deficiencies, CVID can result in frequent bacterial infections, typically involving the ears, sinuses and airways. Many CVID patients experience several bouts of pneumonia, according to NICHD and some develop infections in joints, bones and skin. About a quarter of the people with CVID develop immune system illnesses, including anemia and rheumatoid arthritis. (Read about "Anemia" "Rheumatoid Arthritis") They also have an increased risk of cancer. Disorders of the digestive tract are common. In addition to diarrhea caused by Giardia parasites (Read about "Diarrhea"), people with CVID are prone to inflammatory bowel diseases such as ulcerative colitis or even colon cancer. (Read about "Ulcerative Colitis" "Colorectal Cancer") Many have an enlarged spleen (Read about "The Spleen") and swollen lymph glands (Read about "The Lymph System"), and some develop lymph system cancer (Read about "Lymphoma").
• X-Linked Agammaglobulinemia (XLA): Youngsters with XLA make no antibodies at all, according to NICHD. It is called X-linked because the mutated gene responsible for the disease is located on the X chromosome. As an X-linked disease, XLA affects only males. For their first few months, baby boys who have inherited XLA are healthy, protected by IgG they received from their mothers via the placenta before birth and in the breast milk (Read about "Breastfeeding") after birth. As the mother's IgG fades, however, the baby develops a steady stream of infections. They get infections caused by bacteria that would normally be controlled by antibodies - ear infections, sinus infections, eye infections, skin infections and pneumonia. They can also develop encephalitis, meningitis or blood poisoning/sepsis. (Read about "Encephalitis & Meningitis" "Sepsis") Antibiotics clear up one infection, only to have another start up soon. Boys with XLA are also susceptible to viruses that are normally neutralized by antibodies during their spread in the bloodstream. These include common viruses that cause diarrhea as well as viruses that cause liver disease (Read about "Diarrhea" "The Liver") and polio. There are other X-linked PIs such as X-Linked Severe Combined Immunodeficiency, X-Linked Lymphoproliferative and X-linked Hyper IgM Syndrome, which occur almost exclusively in males. X-Linked Severe Combined Immunodeficiency is described by NIH as the most common of these four disorders, affecting an estimated one in every 50,000 to 100,000 births. (Read more about Severe Combined Immunodeficiency and Hyper IgM Syndrome below.)
• Hyper IgM (Immunoglobulin M) Immunodeficiency: NIH lists this as a rare PI disorder seen most often in males. Immunoglobulin M (IgM) is the first to respond to an invading germ. IgM antibodies tend to stay in the bloodstream, where they aid in killing bacteria. People with Hyper IgM have high levels of IgM; however, they have no IgA, the class of antibody found in body fluids such as saliva, mucus and tears. They also have very low levels of IgG, the common immunoglobulin in the blood. Symptoms include recurring upper and lower respiratory infections within the first year of life. (Read about "Respiratory System") Other signs include enlarged tonsils (Read about "Tonsils & Adenoids"), liver and spleen, chronic diarrhea and an increased risk of unusual or "opportunistic" infections.
• Severe Combined Immunodeficiency (SCID): is what most people think of when they hear about PI disease. It is the disease of "the boy in the bubble," who spent his life in an isolation chamber to protect himself from germs. SCID is rare; chances of a child being born with SCID are about one in 500,000 births. Until recent years, it was always fatal. There are several major causes of SCID. Each is caused by a different genetic defect, and each develops along a different pathway. Whatever the underlying problem that causes SCID, the consequences are nearly always the same. The child lacks almost all immune defenses, develops life-threatening infections and needs major treatment to survive beyond infancy.
• Chronic Granulomatous Disease (CGD): is the name given to a group of inherited immunodeficiency diseases caused by faulty phagocytes. Normally, these large white blood cells engulf germs and destroy them. In CGD, phagocytes are unable to produce the oxygen-transporting compounds that they need in order to kill certain types of germs. According to NPI, this very rare PI disorder occurs once in every one million people and is more common in males than females. People with CGD are susceptible to fungal infections and infections of the lymph glands, chest and skin, which can develop into abscesses. There are four types of CGD, each caused by a different gene defect. By their second birthday, most children with CGD will have infections that are unusually frequent or severe. The infections often respond poorly to standard antibiotics, and in some instances, the child may need to be hospitalized for prolonged intravenous antibiotic treatment. A commonplace bacterium such as Staphylococcus aureus, commonly known as "staph" (Read about "Staph and MRSA") or a usually harmless fungus such as Aspergillus may cause skin infections and rashes (Read about "Skin Rash"), liver abscesses, fever and persistent cough. Almost all the youngsters develop lung disease, including pneumonia. (Read about "Pneumonia") CGD can also cause chronic inflammatory conditions, including gum disease, inflammatory bowel disease, and enlarged lymph glands. (Read about "Oral Health" "Crohn's Disease" "Ulcerative Colitis" "The Lymph System") In addition, CGD causes tumor-like masses called granulomas. Granulomas are made up of clusters of white blood cells that continue to collect in infected areas even after the infection is gone. If large and in critical locations, granulomas can obstruct the passage of food through the digestive tract or the flow of urine. (Read about "The Urinary System")

Warning signs

NIH says quick diagnosis and treatment of serious PI disorders is crucial. Most types of PI can be diagnosed with a blood test. (Read about "Laboratory Testing") NIH recommends testing a child if two or more of these warnings signs are evident:

• eight or more new ear infections within a year
• two or more serious sinus infections within a year
• two or more months on antibiotics with little effect
• two or more cases of pneumonia per year
• failure of an infant to gain weight or grow normally
• recurrent deep skin or organ abscesses
• persistent thrush in the mouth or elsewhere on the skin after age 1 (Read about "Thrush")
• need of intravenous antibiotics to clear infections
• two or more deep-seated infections like meningitis or cellulitis (Read about "Cellulitis")
• a family history of immunodeficiency (Read about "Family Health History")

Treatment options

The Immune Deficiency Foundation (IDF) lists several therapies for people with PI diseases including:

• antibiotic therapies - to deal with infections that occur
• gamma globulin infusions - to supply what the body cannot make on its own (Read about "Infusion Therapy")
• bone marrow transplantation - in certain cases, if a suitable donor is available, a bone marrow transplant can be successful to help the body supply its own disease fighting cells (Read about "Transplants")

Other treatments, such as gene therapy, are still in the experimental stage.

Precautions

NICHD says children with PI diseases should not receive live virus vaccines, such as the oral polio, measles and chicken pox (varicella) vaccines. (Read about "Immunizations") It is not even safe to give live virus vaccines to children suspected of immunodeficiency until there is a definitive diagnosis. There is a risk that such vaccines could cause serious illness or even death.