Autoantibodies are a type of antibodies (proteins produced by cells of the immune system called B lymphocytes) which does not recognize the cells and tissues of its own body and attacks them.
Normally, the body's defense system (immune system) is able to distinguish foreign substances (called non-self) from the cells of your body (called self) and produces antibodies only when it senses that it has been exposed to a threat from factors not self such as, for example, bacteria or viruses. When the immune system stops recognizing one or more of the body's normal constituents as its own (self) can produce autoantibodies to destroy its own cells, tissues and / or organs. This causes inflammation, damage and / or dysfunction which can lead to the clinical manifestations of autoimmune diseases.
When they suspect an autoimmune disease, the treating doctor or rheumatologist prescribes tests to look for autoantibodies: their presence in the blood, in fact, can indicate that an autoimmune process is underway.
The type of autoimmune disease and the amount of damage done depend on the type of organs or tissues affected by the autoantibodies:
- only one organ, disorders caused by autoantibodies that mainly affect a single organ, such as, for example, the thyroid gland in Graves' disease or Hashimoto's thyroiditis, are easier to ascertain because they are related to the affected organ
- multiple organs or systems, disorders due to autoantibodies affecting multiple organs may be more difficult to ascertain. The clinical manifestations and the disorders they cause, in fact, are not very specific and vary from person to person and over time. They can include arthritic-type joint pain, fatigue, fever, rash, allergic-like manifestations, weight loss, and muscle weakness. Diseases associated with this type of autoantibody are called systemic autoimmune diseases. Some examples of these diseases are Systemic Lupus Erythematosus (SLE), systemic sclerosis, Sjögren's syndrome, rheumatoid arthritis
Tests for autoantibodies are done on blood taken from a vein in an arm. Tests for autoantibodies are required by the doctor to ascertain (diagnose) an autoimmune disease. In some cases, they are used to assess the severity and course of the disease over time and the effectiveness of the treatments.
Some tests used to identify autoantibodies that can cause systemic autoimmune diseases include:
- antinuclear antibodies (ANA), can be used to assess the presence or course of some autoimmune diseases such as Systemic Lupus Erythematosus (SLE), systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, autoimmune hepatitis, etc.
- nuclear extractable protein antibodies (ENA), an important test to discover autoimmune diseases such as systemic lupus erythematosus, autoimmune connective tissue diseases, polymyositis, antiphospholipid antibody syndrome, Sjögren's syndrome, rheumatoid arthritis
- anti-neutrophil cytoplasmic antibodies (ANCA), their presence is useful for ascertaining primary vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome
- double-stranded DNA antibodies (anti-dsDNA), are present in "80-90% of SLE patients. High levels of these antibodies are also found in other diseases such as rheumatic diseases, chronic active hepatitis, mononucleosis and biliary cirrhosis
- Anti-centromere antibodies (ACA), are correlated with systemic sclerosis
- Anti-histone antibodies, are found mainly in SLE caused by drugs (procainamide, hydralazine, sulfonamides, isoniazid, tranquilizers, anticonvulsants) but also in rheumatoid arthritis, vasculitis, primary biliary cirrhosis
- rheumatoid factor (FR), the main laboratory test for detecting rheumatoid arthritis
- anti-citrulline antibodies (CCP), alongside the rheumatoid factor test in assessing rheumatoid arthritis
- anti-neutrophil cytoplasmic antibodies (ANCA), are involved in autoimmune vasculitis and chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis
- anti-reticulin antibodies (ARA), appear almost exclusively in celiac disease and, with low frequency, in Crohn's disease, Sjögren's syndrome or rheumatoid arthritis
- gastric parietal cell antibodies (APCA), there is a nonspecific positivity in thyroid diseases, in diabetes mellitus and in iron deficiency anemia. They are present in 90% of people with pernicious anemia
- anti-mitochondrial antibodies (AMA), is a test for many autoimmune diseases: primary biliary cirrhosis, chronic active hepatitis, SLE, pernicious anemia, rheumatoid arthritis, Addison's disease
Some autoantibodies are associated with systems or organs:
- anti-cardiolipin antibodies, in the presence of anti-cardiolipin antibodies or other antiphospholipid antibodies in the blood, the presence of antiphospholipid syndrome (APS) may be formulated
- antibodies to beta 2 glycoprotein 1, their presence is useful in the diagnosis of APS
- lupus anticoagulant antibodies (THERE)
Endocrine / metabolic system
- diabetes-related autoantibodies, among them the most important are the autoantibodies to pancreatic insula (ICA), anti-glutamic acid decarboxylase (GAD), anti-insulin (IAA), anti-tyrosine phosphatase (IA-2A), anti-transporter of zinc 8 (ZnT8)
- anti-tissue transglutaminase antibodies (anti-tTG) and anti-gliadin antibodies (AGA), are positive in 92% of celiac people
- intrinsic factor antibodies (IFA), are responsible for the development of pernicious anemia in people with autoimmune atrophic gastritis
- thyroid autoantibodies, for example, anti-TPO antibodies, thyroid-stimulating hormone receptor TSH (Thyroid-stimulating hormone)
- smooth muscle antibodies (ASMA), are present in more than 85% of people with chronic active hepatitis and in about 50% of individuals with primary biliary cirrhosis. Typical is the association with ANA in autoimmune type I hepatitis
- antibodies to liver and kidney microsomes (LKM), are found in people with primary biliary cirrhosis or chronic autoimmune hepatitis, typical is the association with ANA in autoimmune type II hepatitis
- anti-glomerular basement membrane (GBM) antibodies, to ascertain Goodpasture's syndrome, a rare autoimmune disease affecting the kidneys and lungs
- antibodies to acetylcholine receptor (AChR), performed when myasthenia gravis, an autoimmune neuromuscular disease, is suspected
Given the complexity, autoantibody test results need to be interpreted carefully. Not all individuals with an autoimmune disease have detectable autoantibodies, and some may have more than one. The treating physician or rheumatologist specialist will have to evaluate the test results along with the person's present and past health conditions and disorders, in order to confirm whether or not an autoimmune disease is present.
Link Further information
Buzzetti R, Spoletini M, Tiberti C. Specific autoantibodies of autoimmune diabetes: indications for dosage. Diabetes. 2016; 28
Autoimmune Diseases Working Group (GLaPA). Diagnostic pathway for the search for autoantibodies in connectivitis. Diagnostic path presented during the XL AMCLI National Congress. Rimini, 8-11 November 2011