Autoantibody

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An autoantibody is a protein manufactured by the immune system that is directed against one or more of the host's own proteins. Many autoimmune diseases in humans, most notably lupus erythematosus, are caused by such autoantibodies.

Contents 1 What are they ? 2 Why are they done? 3 Anti-Smooth Muscle Antibodies 4 Specificity of auto-antibodies in malaria and the role of polyclonal activation

[edit] What are they ?

Autoantibodies are proteins that attack specific proteins or other substances found in specific tissues or organs of the body. They are created by the immune system when it fails to distinguish between "self" and "non-self." The immune system must be discriminating. It is normally trained to recognize and ignore the body's own cells and to not overreact to non-threatening substances in the environment, such as foods, plants, and animals. At the same time the immune system must be able to create antibodies – proteins that target and fight specific foreign substances and microorganisms that do pose a threat. Sometimes, however, something goes wrong. For some reason the immune system ceases to recognize one or more of the body's normal constituents as "self," creates autoantibodies, and starts to attack its own cells, tissues, and/or organs, causing inflammation and damage. The causes of this mistake are varied and are not well understood. It is thought that some autoantibody production is due to a genetic predisposition combined with an environmental trigger (such as a viral illness or a prolonged exposure to certain toxic chemicals). There is generally not a direct genetic link however. While families may be prone to develop autoimmune conditions, individual family members may have different autoimmune disorders, or may never develop an autoimmune condition. Researchers believe that there may also be a hormonal component as many of the autoimmune conditions caused by autoantibodies are much more prevalent in women of childbearing age.

The type of autoimmune disorder or disease that occurs and the amount of destruction done to the body depends on which systems or organs are targeted by the autoantibodies, and how strongly. Disorders caused by organ specific autoantibodies, those that primarily target a single organ, such as the thyroid in Graves' disease and Hashimoto's thyroiditis, are often the easiest to diagnose as they frequently present with organ related symptoms.

Disorders due to systemic autoantibodies can be much more elusive. Although the associated autoimmune disorders are rare, the signs and symptoms they cause are relatively common. Symptoms may include: arthritis-type joint pain, fatigue, fever, rashes, cold or allergy-type symptoms, weight loss, and muscular weakness. Associated conditions include vasculitis (inflammation of blood vessels) and anemia. Even if they are due to a particular systemic autoimmune condition, the symptoms will vary from person to person, vary over time, vary with organ involvement, and they may taper off or flare unexpectedly. Add to this the fact that a person may have more than one autoantibody, have more than one autoimmune disorder, and/or have an autoimmune disorder without a detectable level of an autoantibody and you have a complex maze that your doctor must often take you through to arrive at a diagnosis.

The diagnosis of disorders associated with systemic autoantibodies starts with a complete medical history and a thorough physical exam. Based on your signs and symptoms, the doctor may request one or more diagnostic studies that will help to identify a specific disease. These studies include:

[[blood tests to detect inflammation, autoantibodies, and organ involvement x-rays and other imaging scans to detect changes in bones, joints, and organs biopsies to look for pathologic changes in tissue specimens As a rule, information is required from multiple sources (rather than a single laboratory test) to accurately diagnose disorders associated with systemic autoantibodies.Some of the most common systemic autoimmune disorders include: Systemic Lupus Erythematosus (SLE, Lupus) Scleroderma (Progressive Systemic Sclerosis, PSS) Sjögren's Syndrome Dermatomyositis (DM) Polymyositis (PM) Mixed Connective Tissue Disease (MCTD) Rheumatoid Arthritis (RA)]]

[edit] Why are they done?

Autoantibody tests may be ordered as part of an investigation of chronic progressive arthritis type symptoms and/or unexplained fevers, fatigue, muscle weakness and rashes. The Antinuclear antibody (ANA) test is often ordered first. ANA is a marker of the autoimmune process – it is positive with a variety of different autoimmune diseases but not specific. Consequently, if an ANA test is positive, it is often followed up with other tests associated with arthritis and inflammation, such as an rheumatoid factor (RF), an erythrocyte sedimentation rate (ESR) , a C-Reactive Protein (CRP), and/or complement levels . A single autoantibody test is not diagnostic, but may give clues as to whether a particular disorder is likely or unlikely to be present. Each autoantibody result should be considered individually and as part of the group. Some disorders, such as SLE may be more likely if several autoantibodies are present, while others, such as MCTD (mixed connective tissue disease) may be more likely if a single autoantibody (RNP - ribonucleic protein) is the only one present. Those who have more than one autoimmune disorder may have several detectable autoantibodies.

Whether a particular autoantibody will be present is both very individual and a matter of statistics. Each will be present in a certain percentage of people who have a particular autoimmune disorder. For instance, up to 80% of those with SLE will have a positive double strand anti-DNA (anti-dsDNA) autoantibody test, but only about 25-30% will have a positive RNP. Some individuals who do have an autoimmune disorder will have negative autoantibody test results, but at a later date – as the disorder progresses - the autoantibodies may develop. Systemic autoantibody tests are used to:

Help diagnose systemic autoimmune disorders. Help determine the degree of organ or system involvement and damage (Along with other tests such as a CBC or CMP) Monitor the course of the disorder and the effectiveness of treatments. There is no prevention or cure for autoimmune disorders at this time. Treatment is used to alleviate symptoms and to help maintain body function. Monitor remissions, flares, and relapses

List of some autoantibodies and commonly associated diseases
vs. double-stranded-DNA = Systemic lupus erythematosus
vs. Ro or La = Systemic lupus erythematosus and neonatal heart block, primary Sjogren's syndrome
vs. Sm = Systemic lupus erythematosus
vs. phospholipid = Antiphospholipid syndrome
vs. SSA or SSB = Sjogren's syndrome
vs. neutrophil cytoplasmic (cANCA) = Wegener's granulomatosis
vs. neutrophil perinuclear (pANCA) = Systemic vasculitides (non-specific)
vs. IgG (Rheumatoid Factor) = Rheumatoid arthritis
vs. neutrophil perinuclear (pANCA) = Polyarteritis nodosa
vs. centromere = CREST syndrome
vs. Scl70 = Systemic sclerosis
vs. smooth muscle = chronic autoimmune hepatitis
vs. mitochondria = primary biliary cirrhosis
vs. nicotinic acetylcholine receptor = myasthenia gravis
vs. voltage-gated calcium channel = Lambert-Eaton syndrome
vs. thyroid peroxidase (microsmal) = Hashimoto's thyroiditis
vs. TSH receptor = Graves' disease
vs. Hu = Paraneoplastic cerebellar syndrome
vs. voltage-gaed potassium channel (VGKC) = Limbic encephalitis

Note: the sensitivity and specificity of various autoantibodies for a particular disease is different for different diseases. See antibody. link title

[edit] Anti-Smooth Muscle Antibodies

Written by Harrriet S. Gilbert, M.D. to MPD-NET Discussion/Support Group 1997

This antibody is an "auto antibody", meaning that it is made by your immune system and directed against your own tissue - in this case your smooth muscle. There are many types of auto-antibodies, many of which are found in the serum but do not appear to be doing damage to the tissue against which they are directed. Some may damage the target tissue.

Over the years I have seen many patients with MPD, some of whom have autoantibodies and a concommitant autoimmune disease. Autoantibodies are present in collagen-vascular diseases and are believed to be the cause of the symptoms and complications of this group of diseases. An elevated sedimentation rate [[]](ESR) is an associated finding in collagen-vascular disease and is indicative of inflammation

[edit] Specificity of auto-antibodies in malaria and the role of polyclonal activation

Sera of 173 individuals living in a malaria endemic region in Upper Volta (Donse village) were screened for the presence of 14 auto-antibodies by the indirect immunofluorescent and/or passive haemagglutination techniques. At least one auto-antibody (AAb) was detected in sera of 72% (124 out of 173) subjects. No differences in the AAb frequency was observed in the sex or age groups. Conversely, a significant relationship between a high frequency of auto-antibodies, high malaria antibody titres and high IgM levels was observed. Antinuclear antibodies (ANA) (87% of total AAb) and particularly those of speckled pattern of fluorescence were by far the most frequently observed. Smooth muscle antibodies (SMA), heart and gastric parietal cell antibodies and thyroglobulin antibodies were found at a normal frequency. This selective increase in the frequency of one AAb (and not of others) cannot, in our opinion, result from a non-specific polyclonal activation. An alternative hypothesis involving both a specific antigenic and a non-specific mitogenic signal is proposed..