Autoimmune disorders

Autoimmunity is a condition in which the immune system mistakenly recognizes host tissue or cells as foreign. (The word “auto” is the Greek word for self.) Because of this false recognition, the immune system reacts against the host components. There are a variety of autoimmune disorders (also called autoimmune diseases).

An autoimmune disease can be very specific, involving a single organ. Three examples are Crohn’s disease (where the intestinal tract is the target), multiple sclerosis (where tissues of the brain are the target), and diabetes mellitus Type I (where the insulin-producing cells of the pancreas are the target).

Other autoimmune disorders are more general and involve multiple sites in the body. One example is rheumatoid arthritis.

Each autoimmune disorder occurs rarely. However, when all the disorders are tallied together, autoimmunity is found to be a disorder that affects millions of people in the United States alone. For example, rheumatoid arthritis alone afflicts approximately 300, 000 Americans (about 30 people per 10, 000).

The causes of autoimmune diseases are not clearly known. However, there are indications that some disorders, or at least the potential to develop the disorders, can be genetically passed on from one generation to the next. Psoriasis is one such example. The environment also has an influence. The way the immune system responds to environmental factors and to infections (e.g., those caused by some viruses) can trigger the development of a disorder. Other factors, which are less understood, include aging, hormones, physiological changes during pregnancy, and chronic stress.

The basis of autoimmunity: The immune system

The immune system defends the body against attack by infectious microorganisms and inanimate foreign objects. Immune recognition and attack of an invader is a highly specific process. A particular immune system cell will only recognize and target one type of invader. The immune system must develop this specialized knowledge of individual invaders and learn to recognize and not destroy cells that belong to the body itself.

Immune recognition depends upon the chemistry of the surface of cells and tissues. Every cell carries protein markers on its surface. The markers—called major histocompatability complexes (MHCs)—identify the cell as to its type (e.g. nerve cell, muscle cell, blood cell, etc.), and also to which organ or tissue the cell comprises. In a properly functioning immune system, the class of immune cells called T cells recognizes the host MHCs. Conversely, if the T cells encounter a MHC that is not recognized as that which belongs to the host, another class of immune cell called B cells will be stimulated to produce antibodies. There are a myriad of B cells, each of which produces a single characteristic antibody directed toward one specific antigen. The binding of an antibody to the antigen on the invading cell or particle initiates a process that destroys the invader.

In autoimmune disorders, the immune system cannot distinguish between “self” cells and invader cells. As a result, the same destructive operation is carried out on the body’s own cells that would normally be carried out on bacteria, viruses, and other invaders. The reasons why immune systems become dysfunctional are still not clearly understood. It is conceded by the majority of immunologists that a combination of genetic, environmental, and hormonal factors contribute to the development of autoimmunity.

A number of other mechanisms may also trigger autoimmunity. A substance that is normally restricted to one part of the body—and so not usually exposed to the immune system—is released into other areas of the body. The substance is vulnerable to immune attack in these other areas. In a second mechanism, the antigenic similarity between a host molecule and a molecule on an invader may fool the immune system into mistaking the host’s component as foreign. Additionally, drugs, infection, or some other environmental factor can alter host cells. The altered cells are no longer recognizable as “self” to the immune system. Finally, the immune system can become damaged and malfunction by, for example, a genetic mutation.

Examples of general autoimmune disorders

Systemic lupus erythematosus

In systemic lupus erythematosus (often known as Lupus), antibodies attack a number of the body’s own different tissues. The disease recurs periodically and is seen mainly in young and middle-aged women. Symptoms include fever, chills, fatigue, weight loss, skin rashes (particularly the classic “butterfly” rash on the face), vasculitis, joint pain, patchy hair loss, sores in the mouth or nose, lymph-node enlargement, gastric problems, and, in women, irregular menstrual periods. About half of those who suffer from lupus develop cardiopulmo-nary problems, and some may also develop urinary problems. Lupus can also affect the central nervous system, causing seizures, depression, and psychosis.

Rheumatoid arthritis

Rheumatoid arthritis occurs when the immune system attacks and destroys the tissues that line bone joints and cartilage. The disorder occurs throughout the body, although some joints may be more affected than others. Initially, the disorder is characterized by a low-grade fever, loss of appetite, weight loss, and a generalized pain in the joints. The joint pain then becomes more specific, usually beginning in the fingers then spreading to other areas (i.e., wrists, elbows, knees, ankles). As the disease progresses, joint function diminishes sharply and deformities occur. A particularly distinctive feature is the “swan’s neck” curling of the fingers.

Generally, the prevalence rate of rheumatoid arthritis is one percent, although women tend to be afflicted 3-5 times as frequently as men. Aboriginal Americans have an even higher prevalence rate of approximately seven percent.

Scleroderma

This disorder, which affects connective tissue, is also called Crest syndrome or progressive systemic sclerosis. Symptoms include pain, swelling, and stiffness of the joints. As well, the skin takes on a tight, shiny appearance. The digestive system becomes involved, resulting in weight loss, appetite loss, diarrhea, constipation, and distention of the abdomen. As the disease progresses, the heart, lungs, and kidneys become involved, and malignant hypertension causes death in approximately 30% of cases.

Goodpasture’s syndrome

Goodpasture’s syndrome occurs when antibodies are deposited in the membranes of both the lung and kidneys, causing both inflammation of kidney glomerulus (glomerulonephritis) and lung bleeding. It is typically a disease of young males. Symptoms are similar to that of iron deficiency anemia, including fatigue and pallor. Symptoms involving the lungs may range from a cough that produces bloody sputum to outright hemorrhaging. Symptoms involving the urinary system include blood in the urine and/or swelling.

Polymyositis and dermatomyositis

These immune disorders affect the neuromuscular system. In polymyositis, symptoms include muscle weakness, particularly in the shoulders or pelvis, that prevents the patient from performing everyday activities. In dermatomyositis, this muscle weakness is accompanied by a rash that appears on the upper body, arms, fingertips, and sometimes on the eyelids.

Ankylosing spondylitis

Immune-system-induced degeneration of the joints and soft tissue of the spine is the hallmark of ankylosing spondylitis. The disease generally begins with lower back pain that progresses up the spine. The pain may eventually become crippling.

Sjogren’s syndrome

Exocrine glands are attacked, resulting in excessive dryness of the mouth and eyes.

Autoimmune disorders of the endocrine glands

Type I (immune-mediated) diabetes mellitus

This disorder is considered to be caused by an antibody that attacks and destroys the insulin-producing islet cells of the pancreas. Type I diabetes mellitus is characterized by fatigue and an abnormally high level of glucose in the blood (a condition called hyperglycemia).

Grave’s disease

The disorder is caused by an antibody that binds to specific cells in the thyroid gland, causing them to make excessive amounts of thyroid hormone. This disease is characterized by an enlarged thyroid gland, weight loss without loss of appetite, sweating, heart palpitations, nervousness, and an inability to tolerate heat.

Hashimoto’s thyroiditis

An antibody that binds to cells in the thyroid gland causes the disorder known as Hashimoto’s thyroiditis. This disorder generally displays no symptoms, but patients can exhibit weight gain, fatigue, dry skin, and hair loss. Unlike Grave’s disease, however, less thyroid hormone is made.

Autoimmune disorders of the blood and blood vessels

Pernicious anemia

Pernicious anemia is a disorder in which the immune system attacks the lining of the stomach, destroying the ability to utilize vitamin B₁₂. Signs of pernicious anemia include weakness, sore tongue, bleeding gums, and tingling in the extremities. Because the disease causes a decrease in stomach acid, nausea, vomiting, loss of appetite, weight loss, diarrhea, and constipation are possible. Also, because Vitamin B₁₂ is essential for the nervous system function, the deficiency of it brought on by the disease can result in a host of neurological problems, including weakness, lack of coordination, blurred vision, loss of fine motor skills, loss of the sense of taste, ringing in the ears, and loss of bladder control.

Autoimmune thrombocytopenic purpura

In this disorder, the immune system targets and destroys blood platelets. It is characterized by pin-head-size red dots on the skin, unexplained bruises, bleeding from the nose and gums, and blood in the stool.

Autoimmune hemolytic anemia

Antibodies coat and lead to the destruction of red blood cells in autoimmune hemolytic anemia. Symptoms include fatigue and abdominal tenderness due to an enlarged spleen.

Vasculitis

A group of autoimmune disorders in which the immune system attacks and destroys blood vessels can cause vasculitis. The symptoms vary, and depend upon the group of veins affected.

Autoimmune disorders of the skin

Pemphigus vulgaris

Pemphigus vulgaris involves a group of autoimmune disorders that affect the skin. This disease is characterized by blisters and deep lesions on the skin.

Autoimmune disorders of the nervous system

Myasthenia gravis

In myasthenia gravis, the immune system attacks a receptor on the surface of muscle cells, preventing the muscle from receiving nerve impulses and resulting in severe muscle weakness. The disease is characterized by fatigue and muscle weakness that at first may be confined to certain muscle groups, but then may progress to the point of paralysis. Patients often have expressionless faces, as well as difficulty chewing and swallowing. If the disease progresses to the respiratory system, artificial respiration may be required.

Diagnosis of autoimmune disorders

A number of different tests can help diagnose autoimmune diseases. A common feature of the tests is the detection of antibodies that react with host antigens. Such tests involve measuring the level of antibodies found in the blood. An elevated amount of antibodies indicates that a humoral immune reaction is occurring. Antibody production is, of course, a normal response of the immune system to an infection. The normal operation of the immune system must be ruled out as the cause for the increased antibody levels. A useful approach is to determine the class of antibody that is present. There are five classes of antibodies. IgG antibody is the class that is usually associated with autoimmune diseases. Unfortunately, IgG is also dominant in normal immune responses. The most useful antibody tests involve introducing the

KEY TERMS

Autoantibody —An antibody that reacts with a person’s own tissues.

Complement system —A series of 20 proteins that “complement” the immune system; complement proteins destroy virus-infected cells and enhance the phagocytic activity of macrophages.

Macrophage —A white blood cell that engulfs invading cells or material and dissolves the invader.

patient’s antibodies to samples of his or her own tissue. If the antibodies bind to the host tissue, it is diagnostic for an autoimmune disorder. Antibodies from a person without an autoimmune disorder would not react to “self” tissue. Tissues from the thyroid, stomach, liver, and kidney are used most frequently in this type of testing.

Treatment of autoimmune disorders

Treatment is specific to the disease and usually concentrates on lessening the discomfort of the symptoms rather than correcting the underlying cause. Treatment also involves controlling the physiological aspects of the immune response, such as inflammation. This is typically achieved using two types of drugs. Steroids are used to control inflammation. There are many different steroids, each having side effects. The use of steroids is determined by the benefits gained by their use versus the side effects produced. Another form of treatment uses immuno-suppressive drugs, which inhibit the replication of cells. By stopping cell division, non-immune cells are also suppressed. This can lead to, for example, side effects such as anemia.

See also Cell death; Immunology.

Resources

BOOKS

Abbus, Abdul K., and Andrew H. Lichtman. Basic Immunology: Function and Disorders of the Immune System. Philadelphia: W. B. Saunders, 2001.

Baron-Faust, Rita, Jill P. Buyon, and Virginia Ladd. The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On with Your Life. New York: McGraw-Hill, 2003.

Moore, Elaine A., Lisa Moore, and Kelly R. Hale. Graves’ Disease: A Practical Guide. Jefferson, NC: McFarland & Company, 2001.

Santamaria, Pere. Cytokines and Chemokines in Autoimmune Diseases (Medical Intelligence Unit, 30). Georgetown, TX: Eurekah.com, Inc., 2002.

OTHER

National Institutes of Health. National Institute of Allergy and Infectious Diseases, 31 Center Drive, MSC 2520, Bethesda, MD 20892–2520. January 10, 2003 <http://www3.niaid.nih.gov/research/topics/autoimmune/> (accessed December 19, 2006).

John Thomas Lohr