Autoimmune disorders are any of a number of disorders caused by a reaction of the body’s immune system against its own cells and tissues. Such disease-producing processes, known as hypersensitivity reactions, are similar to the reactions that occur in allergy, except that in autoimmune disorders the hypersensitivity response is to the body itself rather than to an external substance.
The immune system normally distinguishes “self” from “nonself”. Some lymphocytes (a type of white blood cell) are capable of reacting against self, but these lymphocytes are generally suppressed. Autoimmune disorders occur when there is interruption of the normal control process, allowing such lymphocytes to escape from suppression, or when there is alteration in a particular body tissue meaning that it is no longer recognized as self and is attacked. Bacteria, viruses, and drugs may play a role in initiating an autoimmune disorder in someone who already has a genetic (inherited) predisposition, but in most cases the trigger is unknown.
Autoimmune processes can have various results, such as the destruction of a particular type of cell or tissue, stimulation of an organ into excessive growth, or interference in an organ’s function. Autoimmune disorders are classified into organ-specific and non-organ-specific types. In organ-specific disorders, the autoimmune process is directed mainly against one organ.
Examples include Hashimoto’s thyroiditis (thyroid gland), pernicious anaemia (stomach), Addison’s disease (adrenal glands), and type 1 diabetes mellitus (pancreas). In non-organ-specific disorders, autoimmune activity is towards a tissue, such as connective tissue, that is widespread in the body. Examples of such disorders are systemic lupus erythematosus (SLE) and rheumatoid arthritis.
Initial treatment for any autoimmune disorder is to reduce the effects of the disease by, for example, replacing hormones, such as insulin, that are not being produced. In cases in which the disease is having widespread effects, treatment is also directed at diminishing the activity of the immune system while maintaining the body’s ability to fight disease. Corticosteroid drugs are most commonly used for this purpose but may be combined with other immunosuppressant drugs.
Autoimmune disorders in more detail - non-technical
Autoimmune disorders are conditions in which a person’s immune system attacks the body’s own cells, causing tissue destruction.
Autoimmunity (see: autoimmunity for a detailed technical article) 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 (systemic), 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. According to the American Autoimmune Related Diseases Association, 50 million Americans have an autoimmune disease. Individuals may, and often do, have more than one autoimmune disorder. Autoimmune diseases are more common in women than in men.
Autoimmune disorders include the following:
Systemic lupus erythematosus (SLE). A general autoimmune disease is one 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 produce 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 producing.
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 target 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.
Sjogren’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. Appears to be caused by an antibody that attacks and destroys the islet cells of the pancreas, which produce insulin.
Amyotrophic lateral sclerosis. 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. A rare disorder that sometimes occurs after an infection or an immunization, Guillain-Barre syndrome affects the myelin sheath that covers nerve cells. It causes progressive muscle weakness and paralysis.
Multiple sclerosis. An autoimmune disorder that may involve a virus, it affects the central nervous system, causing loss of coordination and muscle control.
Celiac disease (sprue). A disease in which the body’s reaction to gluten (most commonly found in wheat) causes damage to the intestines that results in poor absorption of nutrients.
Wegener's granulomatosis A rare disorder in which granulomas (nodular collections of abnormal cells), associated with areas of chronic tissue inflammation due to vasculitis (inflammation of the blood vessels) develop in the nasal passages, lungs, and kidneys.
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 (e.g., bacteria, viruses, fungi) and foreign materials (e.g., chemicals, poisons). When the immune system attacks a foreign 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 identify 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 cell with markers identifying it as belonging to the body. Conversely, if the immune system cells do not recognize a cell as ‘‘self,’’ they attach themselves to it and put out a signal that the body has been invaded. This in turn stimulates the production of substances such as antibodies that disable 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 foreign material.
The reasons why immune systems become dysfunctional and fail to recognize the body’s own cells is not well understood. However, most researchers agree that a combination of genetic susceptibility, environmental, and hormonal factors play a role in developing autoimmunity. Researchers also hypothesize that autoimmunity may be triggered by several different mechanisms as follows:
- A substance that is normally sequestered in one part of the body, and therefore not usually exposed to the immune system, is released into the bloodstream where it is attacked.
- The immune system may mistake a component of the body for a similar foreign component.
- Cells of the body may be altered in some way, either by drugs, infection, or other environmental factors, so that they are no longer recognizable as ‘‘self’’ to the immune system.
- The immune system itself may be damaged, such as by a genetic mutation, and therefore becomes dysfunctional.
The symptoms of autoimmune disorders vary. See specific disorder topics for more complete information.
A short summary of symptoms is as follows: include:
Systemic lupus erythematosus (SLE or lupus). 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 experience lupus develop cardiopulmonary problems, and some may develop urinary problems. Lupus can also effect the central nervous system, causing seizures, depression, and psychosis.
Rheumatoid arthritis. Initially this disorder may be characterized by a low-grade fever, loss of appetite, weight loss, and 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 few 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. This disorder usually is 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 (high blood pressure) 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, which 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, diarrhoea, and constipation are possible. Also, because vitamin B12 is essential for the nervous system function, its deficiency brought about 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.
Sjogren’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 vary greatly.
Type I diabetes mellitus. Characterized by fatigue and an the inability to break down glucose, resulting in abnormally high level of glucose in the blood (hyperglycemia).
Amyotrophic lateral sclerosis. 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 difficulty 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. Paresthesia is often present. This disorder affects both sides of the body and may involve paralysis of the muscles that control breathing.
Multiple sclerosis. Like Amyotrophic lateral sclerosis, the first symptom may be clumsiness. Weakness or exhaustion is often reported, as well as blurry or double vision. The individual may experience dizziness, depression, loss of bladder control, and muscle weakness so severe that the patient is confined to a wheelchair.
Celiac disease. Damage to the lining of the small intestine causes immediate difficulties in digesting food that result in diarrhoea, gas, and cramps, and long-term symptoms of vitamin and mineral deficiencies, anaemia, osteoporosis, and weight loss.
A variety of tests are involved in the diagnosis of autoimmune disorders, depending on the particular disease such as blood tests, cerebrospinal fluid analysis, electromyogram (measures muscle function), and magnetic resonance imaging of the brain. Usually, these tests determine the location and extent of damage or involvement. They also 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 (protein triggers) that would give rise to an autoimmune reaction. An elevated amount of antibodies indicates that a general immune reaction is occurring. Since elevated antibody levels also are seen in common infections, infections 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, this is diagnostic for an autoimmune disorder. Antibodies from a person without an autoimmune disorder would not react to ‘‘self’’ tissue.
Treatment of autoimmune diseases is specific to the disease, and usually focuses 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, for example 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 generally is accomplished with two types of drugs. Corticosteroid compounds (e.g., prednisone) are used to control inflammation. There are many different corticosteroids, each having undesirable side effects, especially with long-term use.
The proliferative nature of the immune response is controlled with immunosuppressive drugs (e.g., azathioprine, chlorambucil, cyclophosphamide, methotrexate). These drugs work by inhibiting the replication of cells and, therefore also suppress nonimmune cells, leading to side effects such as anaemia (too few red blood cells). In addition, other drugs may be used to treat symptoms of specific disorders.
Another approach is the use of drugs such as entanercept (Enbrel), imflixmab (Remicade), and adalimumab (Humira) that block the action of tumor necrosis factor (TNF). TNF is a substance that can cause inflammation in the body. These drugs have proved very effective in relieving symptoms in people with rheumatoid arthritis. However, in June 2008, the United States Food and Drug Administration (FDA) began investigating whether these drugs, especially when administered long term to younger patients, caused an increase in cancer, especially lymphoma (cancer of the lymph tissue). As of 2009, the data on potential cancer risks related to these drugs was confusing and difficult to assess because many patients who developed cancer were taking other drugs in addition to TNFs.
Prognosis depends upon the pathology of each autoimmune disease.
Though the mechanisms involved in how these diseases affect the body are known, it is still unclear why the body turns on itself, thus most autoimmune disorders cannot be prevented. Since more women than men are affected by some of these disorders (e.g., lupus), some researchers are looking into hormones as a factor that may be controlled to prevent or slow certain autoimmune disorders. This, gene therapy, and drugs that target specific immune system cells may help prevent or treat autoimmune disorders in the future.