Young woman with the typical "butterfly rash" found in lupus
|Classification and external resources|
|Specialty||Rheumatology, gastroenterology, other|
An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.
The cause is generally unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. Some common autoimmune disease include celiac disease, diabetes mellitus type 1, Graves disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. The diagnosis can be difficult to determine.
Treatment depends on the type and severity of the condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are often used. Intravenous Immunoglobulin may also occasionally be used. While treatment usually improves symptoms they do not typically cure the disease.
About 24 million (7%) of people in the United States are affected by an autoimmune disease. Women are more commonly affected than men. Often they start during adulthood. The first autoimmune diseases were described in the early 1900s.
For a disease to be regarded as an autoimmune disease it needs to answer to Witebsky's postulates (first formulated by Ernest Witebsky and colleagues in 1957 and modified in 1994):
- Direct evidence from transfer of disease-causing antibody or disease-causing T lymphocyte white blood cells
- Indirect evidence based on reproduction of the autoimmune disease in experimental animals
- Circumstantial evidence from clinical clues
- Genetic evidence suggesting "clustering" with other autoimmune diseases
- Autoimmune diseases are incurable
Signs and symptoms
- Damage to or destruction of tissues
- Altered organ growth
- Altered organ function
A substantial minority of the population suffers from these diseases, which are often chronic, debilitating, and life-threatening.
There are more than 80 illnesses caused by autoimmunity. Autoimmune diseases affect approximately 2-5% of the western world's population. Women are found to be more commonly affected than men. Environmental events can trigger some cases of autoimmune diseases such as exposure to radiation or certain drugs which can damage tissues of the body. Infection can also be a trigger of some autoimmune diseases for example Lupus which is thought to be a milder version of an idiopathic disorder where there is an increased production of antihistone antibodies.
The human immune system typically produces both T-cells and B-cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells. When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system. The mechanisms of preventing self-reactive T-cells from being created takes place through Negative selection process within the thymus as the T-cell is developing into a mature immune cell.
Some infections, such as Campylobacter jejuni, have antigens that are similar (but not identical) to our own self-molecules. In this case, a normal immune response to C. jejuni can result in the production of antibodies that also react to a lesser degree with receptors on skeletal muscle (i.e., Myasthenia gravis). A major understanding of the underlying pathophysiology of autoimmune diseases has been the application of genome wide association scans that have identified a degree of genetic sharing among the autoimmune diseases.
Autoimmunity, on the other hand, is the presence of self-reactive immune response (e.g., auto-antibodies, self-reactive T-cells), with or without damage or pathology resulting from it. This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a particular tissue in different places (e.g. Goodpasture's disease which may affect the basement membrane in both the lung and the kidney).
There are many theories as to how an autoimmune disease state arises. Some common ones are listed below.
Cryptic determinants/molecular sequestration
Although it is possible for a potential auto antigen to be geographically sequestered in an immune privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system. However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an autoantigen. This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance. These poorly displayed areas of an antigen are called "cryptic determinants." The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.
The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self. The cross reactive immune response is responsible for the autoimmune disease state. Cross-reactive immune responses to self were first described for antibodies.
Altered glycan theory
According to this theory the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.
The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million. Jacobson's work was updated by Hayter & Cook in 2012. This study used Witebsky's postulates, as revised by Rose & Bona, to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females. The estimated community prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females. Based on a US population of 320 million, the Hayter & Cook data indicate US prevalence at about 14.5 million.
In a report to the US Congress, the National Institutes of Health reported prevalence between 14.7 and 23.5 million. Although the NIH report predates the Hayter & Cook study by 7 years, the NIH low-range number closely matches their estimate. However, there is no substantiation provided for the higher estimate, and no list of diseases, or any reference to a list of diseases, is included in that report.
In both autoimmune and inflammatory diseases, the condition arises through aberrant reactions of the human adaptive or innate immune systems. In autoimmunity, the patient's immune system is activated against the body's own proteins. In chronic inflammatory diseases, neutrophils and other leukocytes are constitutively recruited by cytokines and chemokines, leading to tissue damage.
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- Ronald Asherson, Andrea Doria, Paolo Pauletto, Pulmonary Involvement in Systemic Autoimmune Diseases, Volume 2, 2005, ISBN 978-0-444-51652-7, ISBN 0-444-51652-2
- Ronald Asherson, Doruk Erkan, Steven Levine, The Neurologic Involvement in Systemic Autoimmune Diseases, Volume 3, 2005, ISBN 978-0-444-51651-0, ISBN 0-444-51651-4
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