Genetics and Immune Disorders

Your immune system allows your body to fight off germs and infections and respond to allergens in the environment.

But the immune system doesn’t always work the way it should.

The Immune System - Click to Enlarge

In some immune system disorders, the immune system can't fight off infections. In other disorders, it incorrectly identifies parts of the body as a threat and attacks the body’s cells the same way it would attack an invading germ. This leads to autoimmune disorders like lupus and rheumatoid arthritis.

Genetic roots of immune disorder

Primary immunodeficiencies are immune disorders that are present at birth. They are inherited, which means they are related to genes passed from one generation to another. Severe immune disorders may be obvious right after birth. Other immune disorders may cause only mild symptoms and may not be noticed until later in childhood or early adulthood.

Genes are the building blocks of human growth and development. They dictate many physical characteristics, such as hair and eye color. They also affect the way the immune system grows and responds to infections and threats in the environment.

Researchers are learning more about the genetic roots of immune disorders every day. They now know that genetic differences affect the way that key components in the immune system function. For example, one genetic defect may block certain cells from acting to defend the body, and another defect might prevent the removal of toxic chemicals from the body. Immune system genetic abnormalities can affect many different functions in the body’s ability to fight foreign “invaders.”

These are the important players in the immune system:

• White blood cells. These are cells in the blood that help fight infection. B cell and T cell lymphocytes and NK (natural killer) lymphocytes all fall under this umbrella.

• Antibodies. The body develops special proteins called immunoglobulins (antibodies) as it fights infections. If the same infection arises in the future, antibodies come into play by allowing the body to fight off the germ or infection it was previously exposed to.

• These are the main antibodies and their roles:

  • Immunoglobulin M (IgM) helps fight bacteria.

  • Immunoglobulin G (IgG) coats invading germs so that immune cells can fight them better.

  • Immunoglobulin A (IgA) stays in the mucus membranes and fights germs there.

  • Immunoglobulin E (IgE) plays a role in responding to allergens.

Common genetic immune disorders

Researchers have identified more than 100 inherited immune disorders. By some estimates, one in every 500 people has a genetic immune disorder.

Some of the most common genetic immune disorders (or primary immune deficiencies) are:

• Common variable immune deficiency (CVID). People with CVID may have B cells that don’t produce enough antibodies. They have chronic infections and may also develop autoimmune diseases. Most cases of CVID are not inherited, but in those that are, two abnormal genes—one from each parent—have been inherited.

• X-linked agammaglobulinemia.. This condition is caused by a mutated, or changed, gene on the X chromosome that impairs the body’s ability to make B cells or antibodies. It is found only in males because they do not have a second X chromosome to balance out the abnormality.

• Selective IgA deficiency. People with this deficiency are often normally healthy, but may be unable to make enough IgA. This could be a result of problems with B cell or T cell function. The cause is not yet known, but it does appear to run in families.

• Hyper IgM syndrome. People with this disorder have a mutated, or changed, gene on the X chromosome that prevents their body from making IgA and IgG.

• Hyper IgE syndrome. This is a rare condition in which people have too much IgE. This leads to skin sores and sores on other membranes in the body. These sores can become infected.

• Chronic granulomatous disease. This inherited disorder prevents a type of white blood cell called phagocytes from engulfing and destroying germs, which is the usual function of these large white blood cells.

• Chediak-Higashi syndrome. This is a severe immune disorder that causes defects in several types of cells. One type is the phagocyte, or white blood cell that "eats" bacteria, viruses, and dead or injured body cells. Two other types are melanocytes, the color-producing cells of the skin; and platelets, cells that help the blood clot.

• Ataxia telangiectasia. B cells and T cells are defective in this inherited condition and levels of both IgG and IgA may be low.

• Severe combined immune deficiency. This is the “classic” immune disorder, which occurs because of inheritance of an abnormal gene from one or both parents. A genetic mutation on the X chromosome is the most common type, which affects boys only and prevents both B cell and T cells from working correctly.

• IgG subclass deficiency. In this condition, the body is unable to make one or two of the four different subtypes of IgG, each of which works to fight specific types of infections. Some cases may be the result of an inherited abnormality, but many don’t appear to be inherited.

• Wiskott-Aldrich syndrome. This is a genetic disorder linked to a mutation, or change, in the X chromosome. It causes easy bleeding, increased infections, and eczema in boys.

Signs and symptoms

Symptoms of an immune disorder include:

• Frequent infections that are worse than they are for most people. For example, someone with a primary immune deficiency may have:

  • Eight or more ear infections in a year

  • Two or more sinus infections in a year

  • Two or more bouts of pneumonia in a year

  • Deep abscesses of the skin or organs that keep coming back

  • Two or more bouts of systemic infection, such as a blood infection called septicemia

• Difficulty fighting infections or infections that last a long time. For example:

  • Taking antibiotics for more than one or two months with no success

  • Becoming sick from bacteria or viruses that other people fight off easily, such as yeast infections (thrush) or other fungal infections of the mouth or skin

• Autoimmune disease symptoms, such as aching joints, tissue destruction, and inflammation

• Trouble growing or gaining weight as an infant

Complications

Complications of primary immune deficiency and genetic immune disorders include:

• Chronic infections

• Severe infections

• Impaired development

• Death

Diagnosis

These are some of the tools used to diagnose a genetic immune disorder:

• Review of personal medical history

• Family history

• Blood tests, including tests of immunoglobulin levels

• Assessment of response to certain vaccines, such as pneumococcal vaccine

• Assessment of response to skin tests, such as tetanus and candida

Treatment

Treatment may include:

• Treating existing infections. Antibiotics or antifungal treatments may be needed to treat the current infection. In severe instances, hospitalization may be needed.

• Treating the immune deficiency. Specific treatment strategies will depend on the immune disorder. Treatments may include bone marrow transplants, enzyme replacement therapy, and antibody replacement therapy. Cytokines and growth factors may also need to be used to help the immune system.

• Preventing infection. People who have immune disorders must work hard to avoid infection. Basic hygiene, such as hand washing, is crucial. But it is also important to limit contact with crowds or people who have colds and illnesses. Children with specific immune disorders should not get live virus vaccines, which can cause sickness.

• Long-term follow-up. Immune disorders mean an ongoing risk of infection. Working with your medical team is needed to keep you as healthy as possible.