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Thursday, August 2, 2018

A primer on autoimmune diseases » Manila Bulletin Lifestyle
src: lifestyle.mb.com.ph

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 diseases that are generally considered autoimmune 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%) 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.


Video Autoimmune disease



Definition

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

Maps Autoimmune disease



Signs and symptoms

Autoimmune diseases have a wide variety of different effects. They do tend to have one of three characteristic pathological effects which characterize them as autoimmune diseases:

  1. Damage to or destruction of tissues
  2. Altered organ growth
  3. Altered organ function

It has been estimated that autoimmune diseases are among the leading causes of death among women in the United States in all age groups up to 65 years.

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.


New therapy treats autoimmune disease without harming normal immunity
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Pathophysiology

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 autoantigen to be spatially 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.

Molecular mimicry

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.

Hygiene hypothesis

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune conditions such as asthma.


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Epidemiology

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.


Autoimmune Disease Diagram stock vector. Illustration of death ...
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Research

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.

Mitigation of inflammation by activation of anti-inflammatory genes and the suppression of inflammatory genes in immune cells is a promising therapeutic approach. There is a body of evidence that once the production of autoantibodies has been initialized, autoantibodies have the capacity to maintain their own production.

Stem cell transplantation is being studied and has shown promising results in certain cases.


Autoimmune Disease. Multiple Sclerosis - Immune Cells Attack ...
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History

Traditionally it was believed that the immune system was unable to react against the body's own tissues, a concept described by the German immunologist Paul Ehrlich as "horror autotoxicus". In 1904 this theory was challenged by the discovery of a substance in the serum of patients with paroxysmal cold hemoglobinuria that reacted with red blood cells.


Autoimmune Disease Symptoms and Your Healthh
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References


what is autoimmune disease? - YouTube
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Further reading

Source of article : Wikipedia