What are autoantibodies?

Autoantibodies are antibodies (immune proteins) that mistakenly target and react with a person's own tissues or organs. One or more autoantibodies may be produced when a person has an autoimmune disorder and their immune system fails to distinguish between "self" and "non-self."

Usually the immune system is able to distinguish between foreign substances ("non-self") and the body's own cells ("self"). It produces antibodies only when it perceives that it has been exposed to a threat ("non-self"), such as bacteria or viruses. However, when the immune system ceases to recognize one or more of the body's normal constituents as "self," it may produce autoantibodies that react with its own cells, tissues, and/or organs. This may cause inflammation, damage, and/or dysfunction of organs or systems, leading to signs and symptoms of autoimmune disorders.

Some autoantibodies do not cause tissue injury directly but are thought to be part of an overall immune response that can cause inflammation and damage. Their presence in the blood can indicate that an autoimmune process is ongoing. Examples include antibodies related to celiac disease and type 1 diabetes.

The causes of autoimmunity are varied and are not well understood. While there is not a direct link, it is thought that many cases of autoantibody production are due to a genetic predisposition combined with an environmental trigger, such as a viral illness or prolonged exposure to certain toxic chemicals. Some families have a high prevalence of autoimmune conditions; however, individual family members may have different autoimmune disorders or may never develop one. Researchers believe that there may also be a hormonal component, as many autoimmune conditions are more common in women of childbearing age.

A recent study found that more than 32 million people in the U.S. have autoantibodies and that the prevalence of the most common type of autoantibody, antinuclear antibody (ANA), is highest among women, older individuals, and African-Americans.

The type of autoimmune disease that occurs and the amount of injury done to tissues and organs depend on which systems are targeted by the autoantibodies:

  • Disorders caused by autoantibodies that primarily affect a single organ, such as the thyroid in Graves disease or Hashimoto thyroiditis, are often easier to diagnose. People with these disorders frequently have signs and symptoms related to that organ.
  • Disorders due to systemic autoantibodies, which affect multiple organs or systems, can be much more difficult to diagnose. The signs and symptoms they cause are relatively non-specific and may include arthritis-type joint pain, fatigue, fever, rashes, cold or allergy-type symptoms, weight loss, and muscular weakness. Some people may develop vasculitis or anemia. Signs and symptoms will vary from person to person and they can vary over time, tapering off and then flaring up unexpectedly. To complicate the situation, some people may have more than one autoantibody or even more than one autoimmune disorder. There are also people who have an autoimmune disorder without a detectable level of an autoantibody. These circumstances can make it difficult to identify the prime cause and arrive at a diagnosis.

Autoantibody tests are performed, along with x-rays, other imaging scans, and biopsies, to help diagnose an autoimmune disorder. In some cases, they are used to help evaluate the severity of the condition, monitor progress of the disease, and assess the effectiveness of treatments.

Autoantibody tests may be ordered when a person presents with chronic, progressive arthritic symptoms, fever, fatigue, muscle weakness, and/or a rash that cannot readily be explained.

One of the most commonly ordered tests is the antinuclear antibody (ANA) test. ANA may be positive with a variety of autoimmune diseases, including lupus, Sjögren syndrome, rheumatoid arthritis, and autoimmune hepatitis. When someone has a positive ANA, other autoantibody tests are used to help make a diagnosis. For example, an anti-dsDNA and a panel of 4 or 6 autoantibody tests called extractable nuclear antigens (ENA) are typically ordered. The pattern of results for these autoantibodies helps to determine if a particular autoimmune disorder is likely to be present.

Results of these autoantibody tests must be interpreted with care and in context. This is because not everyone with an autoimmune disease will have detectable autoantibodies. A health practitioner will consider the results in conjunction with an individual's personal and medical history along with signs and symptoms when making a diagnosis.

Systemic autoantibodies

The list below includes some of the autoantibody tests that are used to identify systemic autoimmune disorders. These disorders may cause signs and symptoms associated with inflammation throughout the body.

  • Antinuclear Antibodies (ANA)
  • Antineutrophil Cytoplasmic Antibodies (ANCA)
  • Anti-Double Stranded DNA (anti-dsDNA)
  • Anticentromere Antibodies (ACA)
  • Antihistone Antibodies
  • Cyclic Citrullinated Peptide Antibodies (CCP)
  • Extractable Nuclear Antigen Antibodies (e.g., anti-SS-A (Ro) and anti-SS-B (La), anti-RNP, anti-Jo-1, anti-Sm, Scl-70)
  • Rheumatoid Factor (RF)

Organ-specific autoantibodies

These are examples of autoantibodies associated with certain systems or organs:

Clotting (coagulation) system

  • Cardiolipin Antibodies
  • Beta-2 Glycoprotein 1 Antibodies
  • Antiphospholipid Antibodies (APA)
  • Lupus anticoagulants (LA)

Endocrine/metabolic system

  • Islet Autoantibodies in Diabetes

Gastrointestinal tract

  • Anti-Tissue Transglutaminase (anti-tTG) and Anti-Gliadin Antibodies (AGA)
  • Intrinsic Factor Antibodies
  • Parietal Cell Antibodies

Thyroid

  • Thyroid Autoantibodies (e.g., anti-TPO, TSH receptor antibodies)

Liver

  • Smooth Muscle Antibodies (SMA) and F-actin Antibody
  • Antimitochondrial Antibodies (AMA) and AMA M2
  • Liver Kidney Microsome Type 1 Antibodies (anti-LKM-1)

Kidney

  • Anti-Glomerular Basement Membrane (GBM)

Muscles

  • Acetylcholine Receptor (AChR) Antibodies

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