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Autoimmune Disorders

Autoimmune Disorders

Definition

Autoimmune disorders are conditions in which a person's immune system attacks the body's own cells, causing tissue destruction.

Description

Autoimmunity is accepted as the cause of a wide range of disorders, and it is suspected to be responsible for many more. Autoimmune diseases are classified as either general, in which the autoimmune reaction takes place simultaneously in a number of tissues, or organ specific, in which the autoimmune reaction targets a single organ.

Autoimmune disorders include the following:

  • Systemic lupus erythematosus. A general autoimmune disease in which antibodies attack a number of different tissues. The disease recurs periodically and is seen mainly in young and middle-aged women.
  • Rheumatoid arthritis. Occurs when the immune system attacks and destroys the tissues that line bone joints and cartilage. The disease occurs throughout the body, although some joints may be more affected than others.
  • 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.
  • Grave's disease. Caused by an antibody that binds to specific cells in the thyroid gland, causing them to make excessive amounts of thyroid hormone.
  • Hashimoto's thyroiditis. Caused by an antibody that binds to cells in the thyroid gland. Unlike in Grave's disease, however, this antibody's action results in less thyroid hormone being made.
  • Pemphigus vulgaris. A group of autoimmune disorders that affect the skin.
  • Myasthenia gravis. A condition in which 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.
  • Scleroderma. Also called CREST syndrome or progressive systemic sclerosis, scleroderma affects the connective tissue.
  • Autoimmune hemolytic anemia. Occurs when the body produces antibodies that coat red blood cells.
  • Autoimmune thrombocytopenic purpura. Disorder in which the immune system targets and destroys blood platelets.
  • Polymyositis and Dermatomyositis. Immune disorders that affect the neuromuscular system.
  • Pernicious anemia. Disorder in which the immune system attacks the lining of the stomach in such a way that the body cannot metabolize vitamin B12.
  • Sjögren's syndrome. Occurs when the exocrine glands are attacked by the immune system, resulting in excessive dryness.
  • Ankylosing spondylitis. Immune system induced degeneration of the joints and soft tissue of the spine.
  • Vasculitis. A group of autoimmune disorders in which the immune system attacks and destroys blood vessels.
  • Type I diabetes mellitus. May be caused by an antibody that attacks and destroys the islet cells of the pancreas, which produce insulin.
  • Amyotrophic lateral schlerosis. Also called Lou Gehrig's disease. An immune disorder that causes the death of neurons which leads to progressive loss of muscular control.
  • Guillain-Barre syndrome. Also called infectious polyneuritis. Often occurring after an infection or an immunization (specifically Swine flu), the disease affects the myelin sheath, which coats nerve cells. It causes progressive muscle weakness and paralysis.
  • Multiple sclerosis. An autoimmune disorder that may involve a virus affects the central nervous system, causing loss of coordination and muscle control.

Causes and symptoms

To further understand autoimmune disorders, it is helpful to understand the workings of the immune system. The purpose of the immune system is to defend the body against attack by infectious microbes (germs) and foreign objects. When the immune system attacks an invader, it is very specifica particular immune system cell will only recognize and target one type of invader. To function properly, the immune system must not only develop this specialized knowledge of individual invaders, but it must also learn how to recognize and not destroy cells that belong to the body itself. Every cell carries protein markers on its surface that identifies it in one of two ways: what kind of cell it is (e.g. nerve cell, muscle cell, blood cell, etc.) and to whom that cell belongs. These markers are called major histocompatability complexes (MHCs). When functioning properly, cells of the immune system will not attack any other cell with markers identifying it as belonging to the body. Conversely, if the immune system cells do not recognize the cell as "self," they attach themselves to it and put out a signal that the body has been invaded, which in turn stimulates the production of substances such as antibodies that engulf and destroy the foreign particles. In case of 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 such harmful entities.

The reasons why immune systems become dysfunctional in this way is not well understood. However, most researchers agree that a combination of genetic, environmental, and hormonal factors play into autoimmunity. Researchers also speculate that certain mechanisms may trigger autoimmunity. First, a substance that is normally restricted to one part of the body, and therefore not usually exposed to the immune system, is released into other areas where it is attacked. Second, the immune system may mistake a component of the body for a similar foreign component. Third, cells of the body may be altered in some way, either by drugs, infection, or some other environmental factor, so that they are no longer recognizable as "self" to the immune system. Fourth, the immune system itself may be damaged, such as by a genetic mutation, and therefore cannot function properly.

KEY TERMS

Autoantibody An antibody made by a person that reacts with their own tissues.

Paresthesias A prickly, tingling sensation.

The symptoms of the above disorders include:

  • Systemic lupus erythematosus. Symptoms include fever, chills, fatigue, weight loss, skin rashes (particularly the classic "butterfly" rash on the face), vasculitis, polyarthralgia, patchy hair loss, sores in the mouth or nose, lymph-node enlargement, gastric problems, and, in women, irregular periods. About half of those who suffer from lupus develop cardiopulmonary problems, and some may also develop urinary problems. Lupus can also effect the central nervous system, causing seizures, depression, and psychosis.
  • Rheumatoid arthritis. Initially may be 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, such as the wrists, elbows, knees, and ankles. As the disease progresses, joint function diminishes sharply and deformities occur, particularly the characteristic "swan's neck" curling of the fingers.
  • Goodpasture's syndrome. 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.
  • Grave's disease. 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. This disorder generally displays no symptoms.
  • Pemphigus vulgaris. This disease is characterized by blisters and deep lesions on the skin.
  • Myasthenia gravis. 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. Myasthenia gravis 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.
  • Scleroderma. Disorder is usually preceded by Raynaud's phenomenon. Symptoms that follow include pain, swelling, and stiffness of the joints, and the skin takes on a tight, shiny appearance. The digestive system also 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.
  • Autoimmune hemolytic anemia. May be acute or chronic. Symptoms include fatigue and abdominal tenderness due to an enlarged spleen.
  • Autoimmune thrombocytopenic purpura. Characterized by pinhead-size red dots on the skin, unexplained bruises, bleeding from the nose and gums, and blood in the stool.
  • Polymyositis and Dermatomyositis. In polymyositis, symptoms include muscle weakness, particularly in the shoulders or pelvis, that prevents the patient from performing everyday activities. In dermatomyositis, the same muscle weakness is accompanied by a rash that appears on the upper body, arms, and fingertips. A rash may also appear on the eyelids, and the area around the eyes may become swollen.
  • Pernicious anemia. 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.
  • Sjögren's syndrome. Characterized by excessive dryness of the mouth and eyes.
  • Ankylosing spondylitis. Generally begins with lower back pain that progresses up the spine. The pain may eventually become crippling.
  • Vasculitis. Symptoms depend upon the group of veins affected and can range greatly.
  • Type I diabetes mellitus. Characterized by fatigue and an abnormally high level of glucose in the blood (hyperglycemia).
  • Amyotrophic lateral schlerosis. First signs are stumbling and difficulty climbing stairs. Later, muscle cramps and twitching may be observed as well as weakness in the hands making fastening buttons or turning a key difficult. Speech may become slowed or slurred. There may also be difficluty swallowing. As respiratory muscles atrophy, there is increased danger of aspiration or lung infection.
  • Guillain-Barre syndrome. Muscle weakness in the legs occurs first, then the arms and face. Paresthesias (a prickly, tingling sensation) is also felt. This disorder affects both sides of the body and may involve paralysis and the muscles that control breathing.
  • Multiple sclerosis. Like Lou Gehrig's disease, the first symptom may be clumsiness. Weakness or exhaustion is often reported, as well as blurry or double vision. There may be dizziness, depression, loss of bladder control, and muscle weakness so severe that the patient is confined to a wheelchair.

Diagnosis

A number of tests are involved in the diagnosis of autoimmune diseases, depending on the particular disease; e.g. blood tests, cerebrospinal fluid analysis, electromylogram (measures muscle function), and magnetic resonance imaging of the brain. Usually, these tests determine the location and extent of damage or involvement. They are useful in charting progress of the disease and as baselines for treatment.

The principle tool, however, for authenticating autoimmune disease is antibody testing. Such tests involve measuring the level of antibodies found in the blood and determining if they react with specific antigens that would give rise to an autoimmune reaction. An elevated amount of antibodies indicates that a humoral immune reaction is occurring. Since elevated antibody levels are also seen in common infections, they must be ruled out as the cause for the increased antibody levels.

Antibodies can also be typed by class. There are five classes of antibodies, and they can be separated in the laboratory. The class IgG is usually associated with autoimmune diseases. Unfortunately, IgG class antibodies are also the main class of antibody seen in normal immune responses.

The most useful antibody tests involve introducing the patient's antibodies to samples of his or her own tissue, usually thyroid, stomach, liver, and kidney tissue. If antibodies bind to the "self" tissue, it is diagnostic for an autoimmune disorder. Antibodies from a person without an autoimmune disorder would not react to "self " tissue.

Treatment

Treatment of autoimmune diseases is specific to the disease, and usually concentrates on alleviating or preventing symptoms rather than correcting the underlying cause. For example, if a gland involved in an autoimmune reaction is not producing a hormone such as insulin, administration of that hormone is required. Administration of a hormone, however, will restore the function of the gland damaged by the autoimmune disease.

The other aspect of treatment is controlling the inflammatory and proliferative nature of the immune response. This is generally accomplished with two types of drugs. Steroid compounds are used to control inflammation. There are many different steroids, each having side effects. The proliferative nature of the immune response is controlled with immunosuppressive drugs. These drugs work by inhibiting the replication of cells and, therefore, also suppress non-immune cells leading to side effects such as anemia.

Systemic enzyme therapy is a new treatment that is showing results for rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and other inflammatory diseases. Enzymes combinations of pancreatin, trypsin, chymotrypsin, bromelain, and papain help stimulate the body's own defenses, accelerate inflammation in order to reduce swelling and improve circulation, and break up the immune complexes within the bloodstream. Symptoms have been reduced using this treatment.

Other treatments that hold some promise are irradiation of the spleen and gene therapy. Splenic irradiation is touted to be a safe, alternative for patients with autoimmune blood diseases, especially autoimmune hemolytic anemia, or others with compromised immune systems, such as HIV patients and the elderly. It is reported to have few side effects and seems to be working. Cytokine and cytokine inhibitor genes injected directly into muscle tissue also appear to be effective in treating Type I diabetes mellitus, systemic lupus erythematosus, thyroditis, and arthritis.

Prognosis

Prognosis depends upon the pathology of each autoimmune disease.

Prevention

Most autoimmune diseases cannot be prevented. Though the mechanisms involved in how these diseases affect the body are known, it is still unclear why the body turns on itself. Since more women than men seem to be affected by some of these disorders (e.g. lupus), some researchers are looking into hormones as a factor. This, and gene therapy, may be the preventatives of the future.

Resources

PERIODICALS

Cichoke, Anthony J. "Natural Relief for Autoimmune Disorders." Better Nutrition. 62, no. 6 (June 2000): 24.

Henderson, Charles W. "Gene Therapy Uses Vectors EncodingCytokines or Cytokine Inhibitors (for treatment of autoimmune disorders)." ImmunotherapyWeekly September 27, 2000: pNA.

Riccio, Nina M. "Autoimmune Disorder: When the Body AttacksItself." Current Health 2 26, no. 5 (January 2000): 13.

"Splenic Irradiation Is an Option for Patients with AutoimmuneDisorders and Those with HIV." AIDS Weekly (April 9, 2001): pNA.

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autoimmune disease

autoimmune disease Every second of our lifetime, we are exposed to a large variety of microorganisms in the environment, which are capable of causing fatal diseases. However, normal individuals rarely succumb to such infections and, even if they do, it is usually for a short duration and with limited damage. This is because of an efficient immune system that destroys these organisms and other foreign substances.

An immune response is brought about by two components of the immune system, namely the innate immunity and the acquired or specific immunity, acting in conjunction with each other and with other molecules. Acquired immunity involves the production of antibodies, each specifically designed to combat a particular antigen — a component of the invading substance or organism. For its normal function of defence, five features of the acquired immune system are essential. These are: (i) specificity for distinct antigens; (ii) diversity; (iii) memory; (iv) self-limitation; and (v) discrimination of self from non-self.

It is the last two features which raise the possibility of Dr Jekyll turning into Mr Hyde. Loss of self-limitation or the failure to maintain self-tolerance can actually turn the immune system from playing a defensive role to causing debilitating diseases. A pathological condition arising from uncontrolled or aberrant immune responses is defined as a hypersensitivity reaction, or allergy. Diseases that are caused due to the immune system acting against self-antigens are called ‘autoimmune diseases’, a situation which has been melodramatically described as ‘horror autotoxicus’ by the famous biologist Paul Erlich.

A wide range of diseases have now been classified as having autoimmune causes. At one end of the spectrum of such diseases are conditions like Hashimoto's thyroiditis, where the antibodies are directed against one specific organ (in this case the thyroid gland). At the other end of the spectrum are diseases such as systemic lupus erythematosus (SLE), where the antibodies are directed against the nucleus of the cells, thereby affecting the whole body; in most instances, specific antibodies can be detected circulating in the blood. In another disease condition, known as Goodpasture's syndrome, the autoantibodies bind to components of the membrane that separates air from blood in the alveoli of the lungs and of the glomerular capillaries of kidneys, where filtration occurs. This causes a localized immune reaction and leads to lung haemorrhages and glomerulonephritis. Similarly, in autoimmune haemolytic anaemia antibodies are directed against red blood cells, enhancing breakdown and phagocytosis of the cells.

In certain cases, however, the autoantibodies do not cause cell damage, but instead alter the normal physiological functions by mimicking normal signalling molecules. For example, in Grave's disease (thyrotoxicosis) autoantibodies bind to the receptors for the thyroid stimulating hormone (TSH) from the pituitary gland and mimic its functions, leading to excessive thyroid hormone production. In another disease, known as myasthenia gravis, autoantibodies bind to the receptors on muscle cells for the neurotransmitter, acetylcholine, and thereby inhibit nerve-to-muscle conduction; over a period of time these receptors are endocytosed (taken up inside the cells) and degraded, causing progressive muscle paralysis.

Sometimes, autoimmune diseases may arise because antibodies, which are produced against foreign antigens, cross-react with the body's own proteins (‘self-proteins’). Thus in acute rheumatic fever, which can develop following a throat infection, antibodies against a cell wall protein of streptococcus bacteria may cross-react with an antigen in the person's own cardiac muscle cells. This leads to myocarditis and damage to the valves of the heart. It is also associated with inflammation of the joints and destruction of the joint cartilage brought about by immune responses.

The immune response involves not only the production of antibodies which circulate in the blood, but also the multiple activities of ‘T-cells’, the lymphocytes which have been ‘programmed’ in the thymus gland to recognize specific antigens, and which mediate the ‘cellular’ component of the immune response. In certain autoimmune diseases, it is the T-cells which become auto-reactive. This occurs in some patients with insulin-dependent diabetes mellitus. In these patients, activated lymphocytes and macrophages destroy the insulin-producing cells in the pancreas, which leads to the disorders of metabolism characteristic of this condition. Some types of anaemia are thought to be due to antibodies being generated against factors required for absorption from the gut of vitamin B12, which is essential for maturation of red blood cells.

Besides the examples described, numerous other pathological conditions have also been classified as autoimmune diseases. Extensive research has been conducted to elucidate the mechanisms by which the immune system discriminates between self and non-self, and the transformation from protector to aggressor in certain pathological conditions of autoimmunity.

One of the cardinal features of immunity is the ability to maintain self-tolerance against self-antigens. Its is an actively acquired process, where self-reactive antibodies are prevented from becoming functionally capable of reacting with self-antigens. A negative selection process plays a major role, whereby immature T-cells, specific for self-antigens, are deleted in the thymus. In certain conditions, the clones may survive but are unable to respond to self-antigens. This is known as clonal ignorance. All these mechanisms lead to the capability of the immune system to discriminate between self and non-self.

Despite these several mechanisms for inducing self-tolerance, autoimmunity remains a significant cause of disease in humans. Multiple factors are implicated in the breakdown of self-tolerance. These factors range from genetic predisposition to microbial infections. Autoimmunity can also arise from abnormalities in lymphocytes following failure of the selection process in the thymus. It is proposed that an individual's ‘major histocompatibility’ genes, which determine their ‘HLA type’ (classification based on human lymphocyte antigens, used in determining tissue compatibility for organ transplants), influence thymic selection, implying a genetic role in autoimmunity. Studies of a particular strain of mice, which develops an accelerated, severe form of systemic autoimmunity, revealed a genetic predisposition. Indeed, autoimmune diseases are often said to ‘run in the family’. HLA typing has shown that some individuals have 90 to 100 times the average predisposition to developing the autoimmune condition called ankylosing spondylosis. This may possibly be due to the controlling of T-cell selection and activation by the gene products which determine the HLA type.

Some autoimmune diseases are caused when antibodies or T-cells, stimulated to act against a foreign antigen, recognize a similar molecular component on a self-protein. This ‘molecular mimicry’ is often a cause for autoimmunity, as described earlier in the case of rheumatic fever.

A plethora of causal factors are thus implicated in leading to autoimmunity. Recent advances have also been made in elucidating the mechanisms involved in self-tolerance and generation of autoimmunity; these hold promise for development of effective strategies for management of these debilitating conditions.

Shiladitya Sengupta, and Tai-Ping Fan


See also immune system.

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Autoimmune Disease

Autoimmune Disease

In order for the immune system to protect the body against attack by foreign organisms, it must be able to distinguish between the body's own proteins (autoantigens) and proteins from foreign cells (foreign antigens ). When the immune system turns against autoantigens, thus attacking its own tissues, the resulting condition is an autoimmune disease.

Common autoimmune diseases include:

  • glomerulonephritis, which compromises the filtering ability of the kidney tubules
  • Graves' disease, which stimulates the thyroid to overproduce thyroid hormone
  • rheumatoid arthritis, which destroys joint tissue
  • myasthenia gravis, which interferes with nerve-muscle communication
  • multiple sclerosis, which destroys the fatty myelin coating of nerves
  • systemic lupus erythematosus, which attacks deoxyribonucleic acid (DNA), causing widespread damage in kidneys, heart, lungs, and skin
  • juvenile onset (Type I) diabetes mellitus, which destroys the insulin-producing beta cells of the pancreas, resulting in inability to regulate blood sugar properly.

Theories of Autoimmunity

The cells involved in immune reactions are B lymphocytes (B cells), which develop in the bone marrow, and T lymphocytes (T cells ), which develop in the thymus. Each lymphocyte carries a recognition site for a specific antigen and becomes activated when that antigen is encountered. During development, most of the lymphocytes that could recognize and destroy widely occurring autoantigens are deleted. Tissues bearing these autoantigens are generally safe from subsequent attack by the immune system unless either the autoantigen mutates or the immune system confuses the autoantigen with a foreign antigen. However, some tissue-specific autoantigens are unavailable when lymphocytes are developing in the bone marrow or thymus, and so lymphocytes with receptors for those autoantigens remain viable, posing the threat of tissue destruction in autoimmune diseases.

It is not yet clear why these lingering, self-reactive lymphocytes do not trigger autoimmunity more often, or why autoimmunity occurs when it does. However, there is strong suspicion that infection may play an important role in genetically susceptible individuals. An infection causes the production of inflammatory chemicals. If these are present at the same time that a lymphocyte is presented with its autoantigen by an antigen-presenting cell, the combination could activate self-reactive lymphocytes that were not deleted during development. Destruction of body tissues bearing those autoantigens would follow.

In another possible process, termed "molecular mimicry," a foreign protein bears such similarity to an autoantigen that B cell antibodies or cytotoxic T cells specific for that foreign antigen cross-react with autoantigens, causing tissue destruction. Alternatively, the combination of a foreign antigen with a self-protein can form a new complex capable of activating appropriate T or B lymphocytes to destroy tissues containing the complex.

see also Antibody; Blood Sugar Regulation; Immune Response; T Cells

Patricia L. Dementi

Bibliography

Janeway, Charles A., Jr., Paul Travers, Mark Walport, and J. Donald Capra. Immunobiology: The Immune System in Health and Disease, 4th ed. New York: Elsevier Science Ltd./Garland Publishing, 1999.

Marieb, Elaine Nicpon. Human Anatomy and Physiology, 5th ed. San Francisco: Benjamin Cummings, 2001.

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autoimmune disease

autoimmune disease, any of a number of abnormal conditions caused when the body produces antibodies to its own substances. In rheumatoid arthritis, a group of antibody molecules called collectively RF, or rheumatoid factor, is complexed to the individual's own gamma globulin blood proteins; the circulating complex apparently causes tissue inflammation and muscle and bone deformities. In Hashimoto's thyroiditis, an inflammatory disease of the thyroid gland, antibodies are produced against the thyroid protein thyroglobulin. In some blood disorders, antibodies may be produced against the body's own red and white blood cells. Myasthenia gravis, a disease characterized by weakened muscles, is thought to have an autoimmune origin. In systemic lupus erythematosus it has been shown that individuals have antibodies to certain of their own body substances that for some reason are acting as antigens; these substances include the individual's own nucleic acids and cell organelles such as ribosomes and mitochondria. Lupus can cause dysfunction of many organs, including the heart, kidneys, and joints. Because lupus and certain diseases of probable autoimmune origin, e.g., scleroderma and dermatomyositis, affect collagen (connective tissue) throughout the body and blood vessels, they are referred to as collagen-vascular diseases. In rheumatic fever, the individual produces antibodies to antigens of streptococcal bacteria; it is believed that the streptococcal antigens are structurally similar to antigens of the heart and that antistreptococcal antibodies, combining with antigenic sites on the heart, damage the muscle and heart valves. Diseases of the immune system are currently treated by a variety of nonspecific immunosuppressive drugs and steroids.

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Autoimmune Disorders

AUTOIMMUNE DISORDERS

DEFINITION


Autoimmune disorders are conditions in which a person's immune system (the network of organs, tissues, cells, and chemicals whose job it is to protect the body from foreign invaders, like bacteria and viruses) attacks the body's own cells. As cells are killed, tissues begin to die off.

DESCRIPTION


Many forms of autoimmune disorders are now recognized. These disorders are classified as general or organ specific. A general autoimmune disorder is one that attacks a number of tissues throughout the body. An organ specific disorder attacks only one type of organ at a time.

Some examples of autoimmune disorders include:

  • Systemic lupus erythematosus (pronounced LOO-puhs er-uh-THEM-uhtuhs; see lupus entry) is a general autoimmune disorder. The condition occurs primarily in young and middle-aged women.
  • Rheumatoid (pronounced ROO-muh-toid) arthritis (see arthritis entry) is inflammation of joints. It occurs when the immune system attacks and destroys tissue that lines the bone joints and cartilage.
  • Goodpasture's syndrome is an inflammation of the lungs and kidneys. It occurs primarily in young males.
  • Grave's disease affects the thyroid gland. The diseases causes the gland to make an excessive amount of thyroid hormone.
  • Hashimoto's thyroiditis also affects the thyroid gland. But it causes a reduction in the amount of thyroid hormone produced by the gland.
  • Pemphigus vulgaris (pronounced PEM-fi-guhs vuhl-GARE-uhs) is a group of autoimmune disorders that affects the skin.
  • Myasthenia (pronounced MY-uhs-THEE-nee-uh) gravis is caused when messages from nerve cells to muscles are disrupted. Muscles become weakened.
  • Scleroderma (pronounced SKLEER-uh-DIR-muh) causes a toughening and hardening of connective tissue.
  • Autoimmune hemolytic anemia is a condition that causes damage to red blood cells (see anemia entry).
  • Autoimmune thrombocytopenic purpura (pronounced THROM-buh-SI-tuh-PEE-nick PIR-puh-ruh) results in destruction to blood platelets, cells that help blood to clot.
  • Pernicious anemia develops when the body can no longer make use of vitamin B12, resulting in a decreased production of red blood cells (see anemia entry).
  • Sjögren's (pronounced SHO-grenz) syndrome occurs when glands are damaged, increasing the loss of water by the body and causing excessive dryness.
  • Ankylosing spondylitis (pronounced ANG-kuh-lozing spon-duh-LIE-tis) results in the destruction of joints and soft tissue in the spine.
  • Vasculitis is a group of disorders in which blood vessels are destroyed.
  • Type I diabetes mellitus (see diabetes mellitus entry) is caused when the islet cells of the pancreas are damaged, preventing the release of insulin to the body.

CAUSES


Autoimmune disorders occur when the body's immune system becomes confused. Because the immune system is used to fight foreign invaders, under normal circumstances, the immune system is able to tell if a group of cells is part of the body or not. For example, it generally has no problem recognizing that bacteria and viruses do not belong to the body. In such cases, the immune system takes a number of actions to fight off and kill the foreign cells.

Autoimmune Disorders: Words to Know

Anemia:
A medical condition caused by a reduced number of red blood cells, characterized by general weakness, paleness, irregular heart beat, and fatigue.
Antibody:
A chemical made by the immune system to destroy foreign invaders.
General autoimmune disorder:
An autoimmune disorder that involves a number of tissues throughout the body.
Immune system:
A network of organs, tissues, cells, and chemicals designed to fight off foreign invaders, such as bacteria and viruses.
Organ specific disorder:
An autoimmune disorder in which only one type of organ is affected.
Steroids:
A group of naturally occurring substances that are very effective in reducing pain and swelling in tissues.

An important component of the immune system is the production of antibodies. Antibodies are chemicals made by the immune system to destroy foreign invaders. Antibodies are very specific. The immune system makes only one type of antibody for each different foreign invader. For example, there is a very specific antibody for each different virus that gets into the body.

But the immune system sometimes makes mistakes. It may somehow regard cells from its own body as being foreign. In such cases, it takes the same actions against those cells as it does against bacteria, viruses, and other truly foreign organisms. It actually begins to destroy healthy, normal cells in the body. When this happens, an autoimmune disorder results.

ORGAN TRANSPLANTATION

An organ transplantation may be necessary when a person's heart, kidney, lungs, liver, or some other vital organ becomes diseased. In such cases, a second person may offer to donate his or her organ to replace the diseased or damaged organ. Autoimmune disorders can often occur when organs are transplanted from one person to another. The problem is that the patient's immune system may reject the donated organ because it thinks the donated organ is a foreign body. It begins to attack the new organ as it would bacteria, viruses, fungi, or other disease-causing organisms.

Patients who receive transplanted organs are also given immunosuppressant drugs. An immunosuppressant drug is a chemical that reduces the body's natural defenses against foreign bodies. It gives the donated organ a chance to become implanted in the new body and start functioning again.

However, immunosuppressant drugs can cause a different set of problems: they prevent the immune system from doing its normal jobs; a patient becomes much more sensitive to diseases that the immune system is usually able to fight; and patients may become ill very easily. For most patients, though, the tradeoff is well worth it. Without the new, healthy organ and the immunosuppressant drugs to sustain it, they might not live.

SYMPTOMS


Each type of autoimmune disorder has its characteristic symptoms. Some of these symptoms include:

  • Systemic lupus erythematosus: Fever, chills, fatigue, weight loss, skin rashes, patchy hair loss, sores in the mouth or nose, problems with the digestive system, vision problems and, in women, irregular periods. Lupus can also affect the central nervous system, causing seizures, depression, and mental disorders.
  • Rheumatoid arthritis: Mild fever, loss of appetite, weight loss, and, most important, pain in the joints. In advanced stages, rheumatoid arthritis can lead to deformities of the body.
  • Goodpasture's syndrome: Fatigue and paleness. Bleeding may occur in the lungs or the urinary system.
  • Grave's disease: An enlarged thyroid gland, weight loss, sweating, irregular heart beat, nervousness, and an inability to tolerate heat.
  • Hashimoto's thyroiditis: Generally no symptoms.
  • Pemphigus vulgaris: Blisters and deep, open sores on the skin.
  • Myasthenia gravis: General muscle weakness that may develop into paralysis. Chewing, swallowing, and breathing may be difficult.
  • Scleroderma: Pain, swelling, and stiffness of the joints. The skin takes on a tight, shiny appearance. Digestive problems may develop, leading to weight loss, loss of appetite, diarrhea, constipation, and swelling of the abdomen.
  • Autoimmune hemolytic anemia: Fatigue and tenderness in the abdomen.
  • Autoimmune thrombocytopenic purpura: Tiny, red dots on the skin, unexplained bruises, bleeding from the nose and gums, and blood in the stool.
  • Pernicious anemia: General weakness, sore tongue, bleeding gums, and tingling in the arms and legs. A deficiency of vitamin B12 can also cause a number of nervous disorders, including weakness, lack of coordination, blurred vision, loss of the sense of taste, ringing in the ears, and loss of bladder control.
  • Sjögren's syndrome: Excessive dryness of the mouth and eyes.
  • Ankylosing spondylitis: Lower back pain that usually moves up the spine.
  • Vasculitis: Symptoms range widely depending on the part of the body affected.
  • Type I diabetes mellitus: Fatigue and an abnormally high level of sugar in the blood.

DIAGNOSIS


The first step in diagnosing any autoimmune disorder is usually a review of symptoms. An additional step involves ruling out other medical conditions that might produce similar symptoms.

The final diagnosis for an autoimmune disorder, however, usually involves a blood test. The purpose of the blood test is to look for antibodies. If ankylosing spondylitis is present in the body, for example, very specific antibodies for that disorder will be present. If no such antibodies are found in the patient's blood, the disorder is not present.

TREATMENT


Treatments differ for each type of autoimmune disorder. However, there is one treatment that is common to many forms of autoimmune disorders. That treatment is the use of drugs to reduce the inflammation, swelling, and pain that accompanies most autoimmune disorders. Inflammation occurs when antibodies attack and irritate tissues. Some common drugs, such as aspirin and ibuprofen (pronounced i-byoo-PRO-fuhn), help reduce inflammation and pain. Aspirin should not be given to children due to the danger of contracting Reye's syndrome (see Reye's syndrome entry). A more powerful medication is one of the many steroid medications. But steroids have some serious long-term side effects, and they are generally used only in severe cases or in situations where milder drugs are ineffective.

PROGNOSIS


Prognosis differs for each type of autoimmune disorder.

PREVENTION


There is currently no way to prevent any of the autoimmune disorders.

See also: Anemias, arthritis, diabetes, and lupus.

FOR MORE INFORMATION


Books

Aaseng, Nathan. Autoimmune Diseases. New York: Franklin Watts, 1995.

Organizations

American Autoimmune Related Diseases Association, Inc. 15475 Gratiot Avenue, Detroit, MI 48205. (313) 3718600. http://www.aarda.org.

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autoimmune disease

autoimmune disease Any one of a group of disorders caused by the body's production of antibodies which attack the body's own tissues. One example of such an autoimmune disease is systemic lupus erythematosus (SLE), an inflammation of the connective tissue occurring most often in young women. The occasional presence of so-called auto-antibodies in an individual does not necessarily indicate autoimmune disease.

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autoimmune disease

autoimmune disease (aw-toh-i-mewn) n. one of a group of otherwise unrelated disorders caused by inflammation and destruction of tissues by the body's own immune response. These disorders include pernicious anaemia, rheumatic fever, rheumatoid arthritis, glomerulonephritis, myasthenia gravis, and Hashimoto's disease.

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Autoimmune Disorders

Autoimmune Disorders

Definition

There are more than 80 chronic, often disabling, illnesses that develop when underlying defects in the immune system lead to attack on the body's own organs, tissues, and cells. Autoimmune diseases are classified as either general (the autoimmune reaction takes place simultaneously in a number of tissues) or organ specific (the autoimmune reaction targets a single organ).

Description

While many of these diseases are rare, together they affect approximately 15 to 24 million people in the United states. The prevalence of autoimmune disorders is rising, although the reasons why are not known. Patients may face a lifetime of illness and treatments because cures are not yet available for most autoimmune diseases. Patients with autoimmune diseases often endure disabiling symptoms, loss of organ function, decreased productivity at work, and costly medical expenses. Since most of these diseases disproportionately affect women, and are among the leading causes of death for young and middle-aged women, the burden is considerable on families and society. Overlapping genetic traits increase susceptibility to many autoimmune diseases, so a person may suffer from more than one autoimmune disorder, or multiple autoimmune diseases may occur in the same family.

Autoimmune disorders include the following:

  • Systemic lupus erythematosus. A general autoimmune disease in which antibodies attack a number of different tissues. The disease recurs periodically and is seen mainly in young and middle-aged women.
  • Rheumatoid arthritis. Occurs when the immune system attacks and destroys the tissues that line bone joints and cartilage. The disease occurs throughout the body, although some joints may be more affected than others.
  • 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.
  • Grave's disease. Triggered by an antibody that binds to specific cells in the thyroid gland, causing them to make excessive amounts of thyroid hormone.
  • Hashimoto's thyroiditis. Also referred to as autoimmune thyroiditis and chronic lymphocytic thyroiditis; a chronic inflammatory glandular autoimmune disease. It is caused by an antibody that binds to cells in the thyroid gland. Unlike in Grave's disease, however, this antibody's action results in less thyroid hormone being made.
  • Pemphigus vulgaris. A group of autoimmune disorders that affect the skin.
  • Myasthenia gravis. A condition in which 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.
  • Scleroderma. Also called CREST syndrome or progressive systemic sclerosis, scleroderma affects the connective tissue.
  • Autoimmune hemolytic anemia. Occurs when the body produces antibodies that coat red blood cells.
  • Autoimmune thrombocytopenic purpura. Disorder in which the immune system targets and destroys blood platelets.
  • Polymyositis and dermatomyositis. Immune disorders that affect the neuromuscular system.
  • Pernicious anemia. Disorder in which the immune system attacks the lining of the stomach in such a way that the body cannot metabolize vitamin B12.
  • Sjögren's syndrome. Occurs when the exocrine glands are attacked by the immune system, resulting in excessive dryness.
  • Ankylosing spondylitis. Immune-system induced degeneration of the joints and soft tissue of the spine.
  • Vasculitis. A group of autoimmune disorders in which the immune system attacks and destroys blood vessels.
  • Type I diabetes mellitus. May be caused by an antibody that attacks and destroys the islet cells of the pancreas that produce insulin.

Causes and symptoms

The symptoms of the above disorders include:

  • Systemic lupus erythematosus. Symptoms include fever, chills, fatigue, weight loss, skin rashes (particularly the classic "butterfly" rash on the face), vasculitis, polyarthralgia, patchy hair loss, sores in the mouth or nose, lymph-node enlargement, gastric problems, and, in women, irregular periods. About half of those who suffer from lupus develop cardiopulmonary problems, and some may also develop urinary problems. Lupus can also effect the central nervous system, causing seizures, depression, and psychosis.
  • Rheumatoid arthritis. Initially may be 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, such as the wrists, elbows, knees, and ankles. As the disease progresses, joint function diminishes sharply and deformities can occur, particularly the characteristic "swan's neck" curling of the fingers.
  • Goodpasture's syndrome. 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.
  • Grave's disease. 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. This disorder generally displays no symptoms. If symptoms do occur, it is most often weight gain, intolerance to cold, fatigue, enlarged neck or goiter, and constipation. About 25% of patients may be subject for developing pernicious anemia, diabetes, adrenal insufficiency, or other autoimmune diseases.
  • Pemphigus vulgaris. This disease is characterized by blisters and deep lesions on the skin. It is associated with other autoimmune diseases, such as systemic lupus and myasthenia gravis.
  • Myasthenia gravis. 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. Myasthenia gravis 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.
  • Scleroderma. Disorder is usually preceded by Raynaud's phenomenon. Symptoms that follow include pain, swelling, and stiffness of the joints, and the skin takes on a tight, shiny appearance. The digestive system also 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.
  • Autoimmune hemolytic anemia. May be acute or chronic. Symptoms include fatigue and abdominal tenderness due to an enlarged spleen.
  • Autoimmune thrombocytopenic purpura. Characterized by pinhead-size red dots on the skin, unexplained bruises, bleeding from the nose and gums, and blood in the stool.
  • Polymyositis and dermatomyositis. In polymyositis, symptoms include muscle weakness, particularly in the shoulders or pelvis, that prevents the patient from performing everyday activities. In dermatomyositis, the same muscle weakness is accompanied by a rash that appears on the upper body, arms, and fingertips. A rash may also appear on the eyelids, and the area around the eyes may become swollen.
  • Pernicious anemia. 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.
  • Sjögren's syndrome. Characterized by excessive dryness and itching of the eyes and dry mouth. Difficulty swallowing, hoarseness, loss of taste, and severe dental caries may also occur. Other symptoms are fatigue, joint pain, and swelling of the glands.
  • Ankylosing spondylitis. Generally begins with lower back pain that progresses up the spine. The pain may eventually become crippling.
  • Vasculitis. Symptoms depend upon the group of veins affected and can range greatly. Some forms of vasculitis may be caused by allergy or hypersensitivity to medications such as sulfa or penicillin, other drugs, toxins, and other inhaled environmental irritants. Other forms may be due to infection, parasites, or viral infections. These causes need to be ruled out before considering an underlying autoimmune disorder.
  • Type I diabetes mellitus. Characterized by fatigue and an abnormally high level of glucose in the blood (hyperglycemia).

To further understand autoimmune disorders, it is helpful to understand the workings of the immune system. The purpose of the immune system is to defend the body against attack by infectious microbes (germs) and foreign objects. When the immune system attacks an invader, it is very specific—a particular immune system cell will only recognize and target one type of invader. To function properly, the immune system must not only develop this specialized knowledge of individual invaders, but it must also learn how to recognize and not destroy cells that belong to the body itself. Every cell carries protein markers on its surface that identifies it in one of two ways: what kind of cell it is (i.e., nerve cell, muscle cell, blood cell, etc.) and to whom that cell belongs. These markers are called major histocompatability complexes. When functioning properly, cells of the immune system will not attack any other cell with markers identifying it as belonging to the body. Conversely, if the immune system cells do not recognize the cell as "self," they attach themselves to it and put out a signal that the body has been invaded, that in turn stimulates the production of substances such as antibodies that engulf and destroy the foreign particles. In case of 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 such harmful entities.

The reasons why the immune systems become dysfunctional in this way is not well understood. However, most researchers agree that a combination of genetic, environmental, and hormonal factors play into autoimmunity. Researchers also speculate that certain mechanisms may trigger autoimmunity. First, a substance that is normally restricted to one part of the body, and therefore not usually exposed to the immune system, is released into other areas where it is attacked. Second, the immune system may mistake a component of the body for a similar foreign component. Third, cells of the body may be altered in some way, either by drugs, infection, or some other environmental factor, so that they are no longer recognizable as "self" to the immune system. Fourth, the immune system itself may be damaged, such as by a genetic mutation, and therefore cannot function properly.

Diagnosis

Autoimmune diseases can affect any part of the body, and have many clinical symptoms that may be difficult to diagnose. There are a number of tests that can help diagnose autoimmune diseases; however, the principle tool used by doctors is antibody testing. Such tests involve measuring the level of antibodies found in the blood and determining if they react with specific antigens that would give rise to an autoimmune reaction. An elevated amount of antibodies indicates that a humoral immune reaction is occurring. Elevated antibody levels are also seen in common infections. These must be ruled out as the cause for the increased antibody levels. The antibodies can also be typed by class. There are five classes of antibodies and they can be separated in the laboratory. The class IgG is usually associated with autoimmune diseases. Unfortunately, IgG class antibodies are also the main class of antibody seen in normal immune responses. The most useful antibody tests involve introducing the patient's antibodies to samples of his or her own tissue—if antibodies bind to the tissue it is diagnostic for an autoimmune disorder. Antibodies from a person without an autoimmune disorder would not react to "self" tissue. The tissues used most frequently in this type of testing are thyroid, stomach, liver, and kidney.

The use of biomarkers could allow earlier diagnosis as well as aid physicians in selecting and monitoring treatment.

Treatment

While treatments are available for many autoimmune diseases, cures have yet to be discovered. Treatment of an autoimmune disease is specific to the disease, and usually concentrates on correction of any major deficiencies. For example, if a gland involved in an autoimmune reaction is not producing a hormone such as insulin, administration of that hormone is required. Administration of a hormone, however, will not restore the function of the gland damaged by the autoimmune disease. The other aspect of treatment is controlling the inflammatory and proliferative nature of the immune response. This is generally accomplished with drugs. Steroid compounds are used to control inflammation. There are many different steroids, each having side effects. Other drugs, Cox-2 inhibitors like celecoxib (brand name Celebrex) are often used to reduce pain and inflammation in rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

The proliferative nature of the immune response is controlled with immunosuppressive drugs. These drugs work by inhibiting the replication of cells and, therefore, also suppress non-immune cells leading to side effects such as anemia. There have been major advances in treatment of some conditions, such as rheumatoid arthritis, using immune-suppressing biological drugs called tumor necrosis factor alpha inhibitors. These drugs are used to treat patients with moderate to severe disease, often when they have not responded to standard therapy. Etanercept (sold under the brand name Enbrel), treats adult onset and juvenile rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Infliximab (brand name Remicade) is indicated for treatment of rheumatoid arthritis, Crohn's disease, psoriatic arthritis, and ankylosing spondylitis. Adalimumab (brand name Humira) is indicated for rheumatoid arthritis and psoriatic arthritis. Abatacept (brand name Orencia) is a novel treatment for rheumatoid arthritis expected to receive approval in early 2006. In many patients, these drugs have provided effective relief from pain and have slowed disease progression, although there can be problems with side effects. Another drug, a B cell depleter called rituximab (brand name Rituxan), is in clinical trials being studied for rheumatoid arthritis, Sjögren's syndrome, and systemic lupus eryththematosus after receiving approval to treat nonHodgkin's lymphoma.

Prognosis

Prognosis depends upon the pathology of each autoimmune disease, as well as early detection and the ability to put the disease process into remission.

Health care team roles

Health care teams should help patients to understand their illness and treatment plan. With any autoimmune disorder, communication between the patient and doctor is critical, so health care teams should be available to answer questions about the patient's particular condition, especially what changes and symptoms to expect.

Prevention

To date, prevention of many autoimmune disorders is unavailable since the exact causes of the disease are not understood in many cases. Genetic screening of an unborn fetus may be the only method of prevention for some autoimmune disorders.

KEY TERMS

Autoantibody— An antibody made by a person that reacts with their own tissues.

Autoimmune disease— A broad category of related diseases in which the person's immune system attacks his or her own tissue.

Researchers are exploring what effects environmental, infectious, and genetic factors play in initiating or exacerbating autoimmune diseases. Discoveries in these areas may lead to new treatments to minimize or reverse the symptoms and manifestations of disease. The knowledge provided by the Human Genome Project will assist in determining the hereditary risks of autoimmune diseases. As more becomes known about the genetic and environmental factors that contribute to autoimmune diseases, effective prevention strategies will be developed to halt the autoimmune process before it can do permanent damage to the body.

Resources

BOOKS

Baron-Faust, Rita and Jill P. Buyon. The Autoimmune Connection. Mount Laurel, NJ: McGraw-Hill, 2004.

Budapest, M., Gershwin, Eric and Yehuda Shoenfeld, ed. Hungary International Conference on Autoimmunity Autoimmune Diseases And Treatment: Organ-Specific And Systemic Disorders (Annals of the New York Academy of Sciences) New York: New York Academy of Sciences, 2005.

Mitchell, Deborah and Stephen B. Edelson What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary, Drug-Free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fatigue; Rheumatoid Arthritis, and Other DiseasesClayton, Australia: Warner Books, 2003.

Rose, Noel R. and Ian R. Mackay Autoimmune Diseases, 4th ed. Burlington, MA: Academic Press, 2006.

Sarzi-Puttini, Piercarlo, Doria, Andrea and Annegret Kuhn. The Skin in Systemic Autoimmune Diseases, Volume 5 (Handbook of Systemic Autoimmune Diseases). Burlington, MA: Elsevier Science, 2006.

Shomon, Mary J. Living Well with Autoimmune Disease: What Your Doctor Doesn't Tell You … That You Need to KnowNew York: HarperCollins Publishers Inc., 2002.

PERIODICALS

Alaedini A, Green PH. "Narrative review: celiac disease: understanding a complex autoimmune disorder." Annals of Internal Medicine. 142 no. 4 (2005):289-98.

Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. New England Journal of Medicine. 350 no. 21 (2004):2167-79.

ORGANIZATIONS

American Autoimmune Related Diseases Association, Inc. National Office. 22100 Gratiot Ave., Eastpointe, MI 48021. (810) 776-3900. 〈http://www.aarda.org〉.

American College of Rheumatology, 1800 Century Place, Suite 250, Atlanta, GA 30345-4300. (404) 633-3777, Fax (404) 633-1870. 〈http://www.rheumatology.org/〉.

Arthritis Foundation, 1330 W. Peachtree St., PO Box 7669, Atlanta, GA 30357-0669. (800) 568-4045. 〈http://www.arthritis.org〉.

National Center for Complementary and Alternative Medicine (NCCAM), 31 Center Dr., Room #5B-58, Bethesda, MD 20892-2182. (800) NIH-NCAM. Fax: (301) 495-4957. 〈http://nccam.nih.gov〉.

U.S. Department of Health and Human Services. 200 Independence Avenue, S.W., Washington, D.C. 20201. (202) 619-0257 or (877) 696-6775. 〈http://www.hhs.gov/〉.

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). 1600 Clifton Rd, Atlanta, GA 30333. (800) CDC-INFO. 〈http://www.cdc.gov/〉. Email: [email protected]

U.S. Department of Health and Human Services, CDC, National Center for Health Statistics, 3311 Toledo Road, Hyattsville, MD, 20782.(866) 441-NCHS (6247). 〈http://www.cdc.gov/nchs/〉. Email: [email protected]

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Autoimmune disorders

Autoimmune disorders

The basis of autoimmunity: The immune system

Examples of general autoimmune disorders

Autoimmune disorders of the endocrine glands

Autoimmune disorders of the blood and blood vessels

Autoimmune disorders of the skin

Autoimmune disorders of the nervous system

Diagnosis of autoimmune disorders

Treatment of autoimmune disorders

Resources

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 Crohns 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 markerscalled 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 bodys 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 bodyand so not usually exposed to the immune systemis 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 hosts 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 bodys 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 swans 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.

Goodpastures syndrome

Goodpastures 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.

Sjogrens 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).

Graves 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.

Hashimotos thyroiditis

An antibody that binds to cells in the thyroid gland causes the disorder known as Hashimotos thyroiditis. This disorder generally displays no symptoms, but patients can exhibit weight gain, fatigue, dry skin, and hair loss. Unlike Graves 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 persons 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.

patients 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 208922520. January 10, 2003 <http://www3.niaid.nih.gov/research/topics/autoimmune/> (accessed December 19, 2006).

John Thomas Lohr

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Autoimmune Disorders

Autoimmune disorders

Definition

Autoimmune disorders are a family of related disorders characterized by the involvement of an inappropriate immune response that leads the body to attack its own cells and tissues.

Description

The immune system consists of the organs and cells of the lymphatic system that protect the body against infections and other diseases. It is the body's defense mechanism against foreign invaders such as harmful microorganisms (pathogens). The sum of the defensive reactions triggered by the presence of a foreign substance or organism in the body is called an immune response. And a foreign substance that can trigger an immune response is called an antigen. The main cells involved in an immune response are white blood cells (leukocytes) called lymphocytes of which two types—the B lymphocytes (B cells) and

T lymphocytes (T cells)—can recognize antigens. The mechanism by which these cells recognize and attack specific antigens is called adaptive immunity, because, after the first response of lymphocytes to a pathogen, some of the B and T cells remain and provide “memory” cells for the immune system to fight the pathogen more effectively when it comes back. The B lymphocytes mature in the bone marrow and produce antibodies, specialized proteins that can attack antigens and help the body destroy them. Antibodies are also called immunoglobulins (Ig) of which there are five main classes: IgA, IgD, IgE, IgG, and IgM. IgG and IgM are the antibodies that protect against infectious diseases . The T lymphocytes mature in the thymus and help B cells to make antibodies and can also attack virus-infected cells and antigens directly.

At birth, an infant only has antibodies that are transferred through the placenta from the mother (passive immunity). Maternal antibodies however, gradually disappear during the first 6–8 months of life. Neonates begin to make their own antibodies at an increased rate soon after birth in response to antigenic stimulation by their “new world.” As a child grows, so does its immune system complement: protective T lymphocytes and new antibodies produced after exposure to specific antigens. The immune system undergoes continuous changes throughout the years. It reaches its peak function at puberty and gradually starts to deteriorate with advancing age (immunosenescence).

In a healthy person, the immune system can distinguish between its own cells and tissues and those that represent foreign threats. Autoimmune disorders are the result of the body producing an inappropriate immune response against its own self, called an autoimmune response, which triggers the production of “autoantibodies” that attack the body's own cells, tissues, or organs

There are more than 80 chronic and often disabling types of autoimmune disorders, either classified as systemic or localized. Some are well known, such as rheumatoid arthritis , multiple sclerosis , type 1 diabetes and systemic lupus while others are less known, such as autoimmune hepatitis and Sjögren's syndrome . Systemic autoimmune disorders are those that damage several organs. Some examples are:

  • Goodpasture's syndrome, affecting lungs and kidneys.
  • Guillain-Barré syndrome, affecting the nervous system.
  • Lupus, affecting skin, joints, kidneys, heart, brain, and red blood cells.
  • Multiple sclerosis, affecting the central nervous system.
  • Polymyalgia rheumatica, affecting large muscle groups.
  • Rheumatoid arthritis, affecting joints.
  • Scleroderma, affecting skin and intestines.
  • Sjögren's syndrome, affecting salivary glands, tear glands, and joints.
  • Wegener's granulomatosis, affecting blood vessels, sinuses, lungs, and kidneys.

Localized autoimmune disorders damage a single organ or tissue type. Some examples are:

  • Addison's disease, affecting the adrenal glands.
  • Autoimmune hepatitis, affecting the liver.
  • Giant cell arteritis, affecting arteries of the head and neck.
  • Graves' disease, affecting the thyroid.
  • Inflammatory bowel disease, affecting the gastroinstestinal tract.
  • Type 1 diabetes , affecting the pancreas.

Life expectancy is continuously rising in all developed countries, leading to an ever-increasing elderly population. But mortality due to infectious disease is greater in the elderly than in the young, partly because of age-associated immunosenescence. As a result, elderly people are more susceptible to infections and are frequently less protected by vaccination. Recent studies in healthy octogenarian patients suggest that two contrasting phenomena occur in immunosenescence: a decrease in the capacity of the immune response and autoantibody production with associated increase in autoimmune disorders.

Demographics

According to a 2005 report by the National Institutes of Health (NIH), many autoimmune disorders are rare, meaning that they affect less than 200,000 people. But collectively, these diseases afflict 14.7 to 23.5 million Americans, an estimated 8% of the population. These disorders disproportionately affect women, and, for reasons unknown, their prevalence is rising.

For some disorders, such as scleroderma , lupus, and Sjögren's syndrome, more than 85% of patients are female. This gender disparity, although smaller, is still observed in other autoimmune disorders, such as multiple sclerosis and inflammatory bowel disease. A few diseases, such as type 1 diabetes, affect men and women almost equally. The reasons for the gender disparity are not well understood, but the production of sex hormones is now thought to represent an important factor.

Americans of African origin seem to be at higher risk than Americans of European origin for lupus and scleroderma, but are at lower risk for type 1 diabetes and multiple sclerosis. High rates of certain autoimmune diseases have also been reported in specific Native American groups. Asian Americans living in Hawaii have some of the lowest rates reported for multiple sclerosis and type 1 diabetes, but these rates seem to increase in those who move to the United States mainland.

Causes and symptoms

The cause of autoimmune disorders is unknown, but all these disorders result from malfunctions of the mechanisms that regulate immune system function. It appears that multiple factors are likely to be involved, with research increasingly suggesting an inherited predisposition to develop autoimmune disease. Environmental factors include viruses , certain drugs, and sunlight, all of which may damage or alter normal body cells. Since 1998, the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) oversee research programs calling for researchers to identify the genetic and environmental factors that lead to autoimmune diseases and to investigate the relationship between them with other studies focused on examining what happens to the immune system during autoimmune disorders.

Many autoimmune diseases share similar symptoms, and many symptoms are not specific to these disorders. Systemic autoimmune disorders also affect many parts of the body. Symptoms of some specific disorders include:

  • Addison's disease: Abdominal pain, decreased body hair, dehydration, diarrhea or constipation, dizziness, fatigue, dark patches of skin (hyperpigmentation), joint and muscle aches, low blood pressure, salt craving, weight loss.
  • Autoimmune hepatitis: Enlarged liver, jaundice, itching, abnormal blood vessels on the skin (spider angiomas), skin rashes, joint pain, fatigue, dark urine.
  • Giant cell arteritis: Headache, scalp tenderness, loss of vision, facial pain.
  • Goodpasture's syndrome: Bloody or dark urine, decreased urination, cough with bloody sputum, low-grade fever, difficulty breathing after exertion, weakness, fatigue, nausea or vomiting, weight loss.
  • Graves' disease: Mild forms of the disease can include symptoms such as nervousness, heat intolerance, diarrhea, sweating, insomnia, and weight loss with increased appetite. More serious cases may include irregular heartbeat, increased heartbeat (tachycardia), tremor and atrial fibrillation, extreme sensitivity to light, swelling in the legs and eyes, and clubbing of the fingers.
  • Guillain-Barré syndrome: Muscle weakness, paralysis, spasms, numbness, tingling or pins-and-needle sensations, and/or tenderness.
  • Inflammatory bowel disease: Severe and persistent inflammation of the lining or wall of the gastrointestinal tract. Chronic, bloody diarrhea.
  • Lupus: Appearance of small or moderate-sized, coin-shaped red patches usually on exposed areas of the body, such as the face, scalp, ears, chest, and arms.
  • Polymyalgia rheumatica: Pain and weakness in the neck, shoulder muscles and pelvis, morning stiffness.
  • Rheumatoid arthritis: Inflammation and thickening of the tissue that lines the joints, most commonly the small joints of the hands resulting in pain and swelling.
  • Scleroderma: Appearance of one or more patches of hardened and thickened skin (sclerosis). In some forms, presence of tight, glossy skin on the trunk and upper arms as well as on the face, chest and extremities.
  • Sjögren's syndrome: Dry mouth and eyes, swollen salivary glands, feeling of sand or grit in the eyes, difficulty swallowing, joint pain, and decreased sense of taste.
  • Type 1 diabetes: High blood sugar levels (hyperglycemia), increased thirst and urination, dehydration, fatigue, nausea, vomiting, increased appetite, weight loss, blurred vision, numbness, tingling, and pain in the feet.
  • Wegener's granulomatosis: Chronic, progressive inflammation of the upper and lower respiratory tract. The inflammation may form lumps (granulomas) in the tissues or in the skin and may progress into generalized inflammation of the blood vessels (vasculitis) and kidneys (glomerulonephritis).

Diagnosis

Since there are so many types of autoimmune disorders, diagnosis is often hard to establish. Another difficulty is that the symptoms of many autoimmune disorders—such as fatigue or diarrhea—also occur in other diseases. It also happens that a person may have more than one autoimmune disease. For instance, patients with Addison's disease often also have type 1 diabetes and Giant cell arteritis is found in approximately 50% of the patients with polymyalgia. A detailed history of symptoms, and a complete physical examination are accordingly essential to start establishing diagnosis in combination with blood and urine tests. Other tests are required to diagnose autoimmunity and measure inflammation and organ function. Serological assays which can detect specific autoantibodies are used to diagnose several systemic autoimmune disorders while localised disorders are often diagnosed by immunofluorescence of biopsy specimens. For instance, blood tests for thyroid stimulating hormone (TSH) can help diagnose Graves' disease. One of the hallmarks of an autoimmune disorder is the production of antinuclear antibodies by the body and the antinuclear antibody (ANA) test can establish the pattern and level of these antibodies to help define the type of disorder. Laboratory test results however, are often inadequate to confirm a diagnosis. For example, a test for the presence of an antibody called rheumatoid factor (RF) can be used to help diagnose rheumatoid arthritis. However, some people with RF never get the disease, while others with the disease never have RF.

Treatment

While treatments are available for many autoimmune diseases, cures have yet to be discovered. The current goal for patients with autoimmune disorders is to find treatments that produce remissions with fewer side effects. Medical practitioners most often help patients manage the consequences of inflammation caused by the autoimmune disease. For example, physicians prescribe insulin for type 1 diabetes to control blood sugar levels so that high blood sugar will not damage the kidneys, eyes, blood vessels, and nerves. In other disorders, such as lupus or rheumatoid arthritis, medication can be prescribed to suppress the autoimmune destruction of the kidneys or joints. These medications are called immunosuppressants and include corticosteroids (prednisone), methotrexate, cyclophosphamide, azathioprine, and cyclosporin. However, they have potentially serious side effects, such as also suppressing the ability of the immune system to fight infection.

Nutrition/Dietetic concerns

Autoimmune research has started investigating nutritional factors that affect immune function and interactions between dietary factors and other exposures. For example, reports suggest that antioxidants may play a role in immune function, particularly with respect to autoimmunity. Lupus—prone mice have shown delayed symptom onset or prolonged survival when given antioxidant supplements. The potential role of diet in autoimmune disorders is emerging as an important issue for patients.

Therapy

Research in autoimmune disorders is accelerating with the promise of new therapies that target various steps in the immune response, and new technologies, such as the development of biological markers to enable earlier diagnosis and help physicians to select and monitor treatment. New approaches being developed include the use of therapeutic antibodies against specific T cell molecules which may produce fewer long-term side effects than the medications now in use.

Prognosis

Currently, autoimmune disorders cannot be cured with treatment, although in rare cases they may disappear on their own. Many people experience flare—ups and temporary remissions in symptoms, others chronic symptoms or a progressive worsening. Since cures are not yet available, patients are often faced with a lifetime of illness and treatment. They often endure debilitating symptoms, loss of organ function, and reduced productivity at work, requiring lifelong follow—up. Since the course the disorders take is unpredictable, it makes it very difficult for medical practitioners to foresee what will happen to the patient based on onset symptoms. However, many patients are able to live normal lives if their disorder can be medically managed.

Prevention

Since the cause of autoimmune disorders is not understood, they cannot be prevented. However, increasing knowledge about the genetic and environmental factors contributing to these disorders carries the hope of developing effective prevention strategies to arrest the autoimmune process before it can irreversibly damage the body. A major goal of autoimmune disease research is to identify people at risk before irreversible organ damage occurs. Investigators have recently detected lupus autoantibodies in serum that often are present years before the patient displays symptoms. Serum samples from lupus patients also contained antibodies that reacted with the Epstein—Barr virus, suggesting that a virus may be involved in lupus. In another study on rheumatoid arthritis, high concentrations of autoantibodies and T cells in the blood were found to be predictive of rapid disease progression.

QUESTIONS TO ASK YOUR DOCTOR

  • What type of autoimmune disease could I have?
  • Are there medicines to treat autoimmune diseases?
  • How can I manage my life now that I have an autoimmune disease?
  • What kinds of medical specialists will I need to treat my autoimmune disease?
  • What can I do to feel better?

Caregiver concerns

According to a survey performed by the American Autoimmune Related Diseases Association (AARDA), the majority of patients eventually diagnosed with serious autoimmune diseases had significant problems in obtaining a correct diagnosis. They were often incorrectly diagnosed with a variety of conditions, or told that their symptoms were imaginary, or that they were too stressed. Further, the survey revealed that 45% of autoimmune disease patients had been labelled hypochondriacs in the earliest stages of their illnesses. It is also recognized that, in older patients, autoimmune diseases have higher rates of morbidity and mortality which points to a need for the study of autoimmune manifestations in elderly populations.

Resources

BOOKS

Baron-Faust, Rita, and Jill P. Buyon. The Autoimmune Connection. New York, NY: McGraw-Hill, 2004.

Jackson Nakazawa, Donna. The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance—and the Cutting-Edge Science that Promises Hope. New York, NY: Touchstone (Simon & Schuster), 2008.

Moore, Elaine A. Autoimmune Diseases and Their Environmental Triggers. Jefferson, NC: McFarland & Company, 2002.

Moore, Elaine A., and Lisa Moore. Graves' Disease: A Practical Guide. Jefferson, NC: McFarland & Company, 2001.

Ravicz, Simone. Thriving With Your Autoimmune Disorder: A Woman's Mind-Body Guide. Oakland, CA: New Harbinger Publications, 2000.

Rose, Noel R., and Ian R. Mackay, editors. The Autoimmune Diseases. 4th ed. New York, NY: Academic Press, 2006.

Sticherling, Michael, and Enno Christophers, editors. Treatment of Autoimmune Disorders. New York, NY: Springer, 2003.

KEY TERMS

Adaptive immunity —The response of lymphocytes to specific antigens. After the first response of lymphocytes to a pathogen, B and T cells remain to fight more effectively against the pathogen if it ever returns. Also called acquired immunity.

Antibody —A protein produced by the body's immune system in response to a foreign substance.

Antigen —Any foreign substance, usually a protein, that stimulates the body's immune system to produce antibodies.

Antinuclear antibody (ANA) test —A test that measures the amount and pattern of antibodies in the blood that work against a person's own body.

Antioxidant —A substance, such as vitamin E, vitamin C, or beta carotene, thought to protect body cells from the damaging effects of oxidation.

Autoantibody —An antibody produced in the body that attack its own cells, tissues, and/or organs.

Autoimmune response —A condition in which a person's immune system fails to recognize its own cells as being “self” and attacks its own body.

Autoimmunity —Condition in which the immune system reacts against the body's own tissue.

Biological marker —Measurable and quantifiable biological parameters that can be used to diagnose a disease accurately.

Immune —Resistant to a given disease.

Immune response —The activity of the immune system against antigens.

Immune system —The organs and cells that defends the body against infections and other diseases.

Immunity —The condition of being immune.

Immunoglobulin (Ig) —A substance made by B cells that neutralizes specific disease—causing substances and organisms. Also called “antibody.” Immunoglobulins are divided into five classes: IgA, IgD, IgE, IgG, and IgM.

Immunofluorescence —Test that labels antibodies or antigens with fluorescent dyes to visualize the contents of cells.

Immunosenescence —Aging of the immune system.

Immunosuppressant —A medicine that blocks the body's immune response.

Inflammatory bowel disease —Inflammation of the colon and rectum. Inflammatory bowel disease includes Celiac disease, Crohn's disease, and ulcerative colitis.

Leukocyte —White blood cell.

Lymphatic system —The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease.

Lymphocytes —Leukocytes involved in the immune response. They include B cells, T cells, and natural killer cells.

B lymphocytes (B cells) —Lymphocytes that produce antibodies.

T lymphocytes (T cells) —Lymphocytes that recognize foreign substances and process them for removal.

Microorganism —An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi.

Passive immunity —Immunity produced by providing a person with antibodies from another source than self.

Pathogen —A disease—causing microorganism.

Thymus —An organ that is part of the lymphatic system and in which T lymphocytes grow and multiply. It is located in the chest behind the breastbone.

PERIODICALS

DeVeale, Brian, et al. “Immunity and aging: the enemy within?” Aging Cell 3, no. 4 (2004): 195–208.

Diep, J. T., and P. D. Gorevic. “Geriatric autoimmune diseases: systemic lupus erythematosus, Sjögren's syndrome, and myositis.” Geriatrics 60, no. 5 (May 2005):32–38.

Hakim, F. T., and R. E. Gress. “Immunosenescence: deficits in adaptive immunity in elderly.” Tissue Antigens 70 (2007): 179–189.

Kovaiou, R. D., et al. “Age-related changes in immunity: implications for vaccination in the elderly.” Expert Reviews in Molecular Medicine 9, no. 3 (February 2007): 1–17.

Lesourd, B. “Nutrition: a major factor influencing immunity in the elderly.” Journal of Nutrition, Health & Aging 8, no. 1 (2004): 28–37.

Loo, W. J., and N. P. Burrows. “Management of autoimmune skin disorders in the elderly.” Drugs & Aging 21, no. 12 (2004): 767–777.

Ramos-Casals, M., et al. “Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly.” Lupus 12, no. 5 (2003): 341–355.

OTHER

Autoimmune Disorders. American Association for Clinical Chemistry, Information Page (February 20, 2008). http://www.labtestsonline.org/understanding/conditions/autoimmune.html

Autoimmune Diseases. National Women's Health Information Center, Information Page (February 20, 2008). http://womenshealth.gov/faq/autoimmune.htm

Coping with Autoimmunity. AARDA Information Page (February 20, 2008). http://www.aarda.org/coping_with_autoimmunity.php

Living with Autoimmune Diseases. WomensHealth.gov Information Page (February 20, 2008). http://womenshealth.gov/pub/2007daybook/autoimmune/

ORGANIZATIONS

American Autoimmune Related Diseases Association (AARDA), 22100 Gratiot Ave., Detroit, MI, 48021, (586) 776-3900, (800) 598-4668, [email protected], http://www.aarda.org.

National Institute of Allergy and Infectious Diseases (NIAID), 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 20892-6612, (301) 496-5717, (866) 284-4107, http://www3.niaid.nih.gov.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 1 AMS Circle, Bethesda, MD, 20892-3675, (301) 495-4484, (877) 22-NIAMS, [email protected], http://www.niams.nih.gov.

Monique Laberge Ph.D.

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Autoimmune Disorders

Autoimmune disorders

Autoimmunity is a condition where 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.

The causes of autoimmune disease are not clearly known. However, there are indications that some disorders, or at least the potential to develop the disorder, 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 .


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 cardiopulmonary 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.

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 hallmarks 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 B 12 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 pinhead-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.

The above are only some of the more than 30 autoimmune disorders.


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 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 the 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 .


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 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 immunosuppressive 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 AutoimmuneDiseases (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 [cited January 10, 2003]. <http://www.niaid.nih.gov/publications/autoimmune/autoimmune.tm>.


John Thomas Lohr

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Autoantibody

—An antibody made by a person that reacts with their 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.

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