Autoantibody

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

An autoantibody is an antibody (a type of protein) manufactured by the immune system that is directed against one or more of the individual's own proteins.

Many autoimmune diseases in humans, most notably lupus erythematosus, are caused by such autoantibodies.

Production

Antibodies are normally produced in response to a foreign protein or substance within the body, typically a pathogen (infectious organism). Normally, the immune system is able to recognize and ignore the body's own cells and to not overreact to non-threatening substances in the environment, such as foods.

Sometimes, however, the immune system ceases to recognize one or more of the body's normal constituents as "self," leading to production of autoantibodies. These autoantibodies attack the body's own cells, tissues, and/or organs, causing inflammation and damage.

Cause

The causes of autoantibody production are varied and 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 susceptible to 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 are much more prevalent in women of childbearing age.

Types

Many autoantibodies are recognized. These are some medically important autoantibodies: -

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.

Diseases

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:

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 a 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. Condition
vs. double-stranded-DNA Systemic lupus erythematosus
vs. Exosome complex Scleromyositis
vs. Ro or La Systemic lupus erythematosus and neonatal heart block, primary Sjogren's syndrome
vs. Smith Systemic lupus erythematosus
vs. phospholipid Antiphospholipid syndrome
vs. SSA or SSB Sjogren's syndrome
vs. neutrophil cytoplasmic (c-ANCA) Wegener's granulomatosis
vs. neutrophil perinuclear (p-ANCA) Systemic vasculitides (non-specific)
vs. IgG (Rheumatoid factor) Rheumatoid arthritis
vs. neutrophil perinuclear (pANCA) Polyarteritis nodosa
vs. centromere CREST syndrome
Anti-topoisomerase antibodies 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 (microsomal) Hashimoto's thyroiditis
vs. TSH receptor Graves' disease
vs. Hu Paraneoplastic cerebellar syndrome
vs. voltage-gated potassium channel (VGKC) Limbic encephalitis
vs. N-methyl-D-aspartate receptor (NMDA) Encephalitis

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

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