Antibodies are critical for protecting us from disease-causing bacteria and viruses, but antibodies that target our own bodies can lead to autoimmune disease. In this comprehensive guide, we’ll discuss what autoantibodies are, as well as some common types of autoantibodies and autoimmune diseases. 

What Are Antibodies?

Antibodies, or immunoglobulins, are Y-shaped proteins produced by white blood cells known as B lymphocytes, or B cells. Antibodies make up about 20% of the total protein content of plasma, the part of blood that is left after red and white blood cells and platelets are removed. (Source) 

What Do Antibodies Do?

Antibodies find pathogens and other foreign substances that have entered the body, stick to them, and signal other members of the immune system to come help eliminate them.

Antibodies recognize foreign invaders by molecules the foreigners carry called antigens. Each antibody fits a specific antigen, and the introduction of a new antigen causes B cells to produce new antibodies to match it. This is called the adaptive, or acquired, immune response — the immune system adapts to new challenges.

Where in the body antibodies do their work is determined by their isotype. (Source) 

Antibody Isotypes

Antibodies are formed of strings of smaller proteins known as chains. Light chains are each made up of about 220 amino acids, and heavy chains are each made up of about 440 amino acids. The structure of the heavy chains determine what isotype, or class, of immunoglobulin an antibody is. (Source)

Human antibody heavy chains have 5 isotypes:

• IgM antibodies are sometimes called “natural antibodies” because they aren’t specific to any individual antigen and are the first to respond to a novel threat. (Source)
• IgA antibodies protect mucous membranes in particular. They are the predominant isotype found in colostrum and breast milk. (Source)
• IgD antibodies have been identified but we don’t know much about them or what they do.
• IgE antibodies are associated with allergies and parasitic infections. While allergies in general are not beneficial to health, IgE antibodies seem to treat tumors as allergens, suggesting they hold promise in cancer treatment. (Source)‍
• IgG antibodies are the smallest and, with 4 subtypes, the most numerous antibodies. They pass easily into tissues all over the body and are the only antibodies that cross the placenta. (Source)

What Are Autoantibodies?

The role of antibodies is to protect the body from pathogens and other substances that enter the body from the outside. For antibodies to work properly, the immune system must be able to distinguish between “self” and “nonself” — that is, to tell the difference between foreign invaders and the cells, proteins, and other substances that belong in the body.

Antibodies that lose this ability and mistakenly target the body’s own tissues are called autoantibodies. Autoantibodies may bind with antigens on many different substances in the body, including DNA, RNA, fats, and proteins. These antigens may be found on the surface of cells, inside cells, or in the fluid between cells. In the most common systemic autoimmune diseases, autoantibodies target molecules inside the cell. (Source)

How Autoantibodies Are Activated

Research suggests the onset of autoimmunity involves an interplay of different contributing factors, including genetic predisposition, lifestyle, and environmental exposures. There is evidence for the “multiple hit” theory, which states that one “hit” causes autoantibodies to begin forming, and then at least one other “hit” is needed to activate the autoantibodies so they start attacking. (Source)

These hits may include:

Failure to Clear Apoptotic Debris

Apoptosis is the pre-programmed death of a cell at the end of its life. When a normal cell dies, it presents molecules on its membranes to signal immune cells called phagocytes to come clear it away. If these molecules are changed in a way that causes them to appear to be “nonself,” the immune system may see them as threats and autoimmunity may be activated. Similarly, apoptosis of abnormal cells may release antigens that stimulate an autoimmune response. (Source)

Modification of Self-Antigens by Inflammation

Another theory is that inflammation in the body causes changes in self-antigens that lead to an autoimmune response. This initiates a vicious cycle in which inflammatory modification of self-antigens causes injury to targeted cells, which are then damaged so they release more antigens into circulation, which leads to more injury and more inflammation. (Source)

Infection With a Cross-Reacting Virus

Another possibility under research is that exposure to a virus that presents antigens to the immune system that mimic or resemble self-antigens may stimulate autoantibodies to attack the body’s own cells or other tissues. (Source) 

Some Autoantibodies May Be Natural

The B cells that produce antibodies start out in the blood marrow and mature in the spleen, a small organ tucked up under the stomach, after which they can become activated as part of an immune response elsewhere in the body. B cells that might react to the body’s own tissues generally don’t make it into circulation, but some do slip through. For this reason, it isn’t unusual for healthy people to have some “natural” autoantibodies in their blood. It is thought that natural autoantibodies are present from birth. (Source, Source)

What’s the Connection Between Autoantibodies and Autoimmune Diseases?

While some autoantibodies are natural and they may be present even if you don’t have an autoimmune disease, they can cause autoimmune disease if you are susceptible. The presence of autoantibodies can be a sign that you are genetically predisposed to an autoimmune disease. 

Autoimmune disease is a general term used to describe any condition in which the immune system attacks and destroys healthy cells in the body by mistake. This can affect any tissue or organ in the body, including the skin, joints, blood vessels, muscles, and nervous system.

Although there are over 80 different types of autoimmune diseases, the most common include psoriasis, rheumatoid arthritis, autoimmune thyroid disease (Hashimoto’s and Graves’ diseases), and celiac disease. (Source)

Many autoimmune diseases associated with autoantibodies in the blood are long term and chronic. There may be a relationship between the amount of autoantibodies detected in the blood and the severity of the autoimmune disease. In some autoimmune diseases, such as type 1 diabetes and thyroiditis, autoantibodies may be detected years before any symptoms appear. (Source) 

How Can Testing for Autoantibodies Be Helpful?

Autoantibodies can be used as markers of autoimmune disease activity. In diseases with a long onset, such as type 1 diabetes and thyroiditis, autoantibodies may be detected before symptoms become noticeable. Early testing for autoantibodies can help predict whether and when symptoms are likely to occur, sometimes providing an opportunity to forestall disease through preventive therapy and avoidance of environmental triggers. (Source)

Autoantibodies can also be used to determine whether or not a condition is due to an autoimmune disorder, helping guide treatment and management of symptoms.

What Do We Need to Know About Predictive Tests?

Because autoantibodies are sometimes detected before symptoms begin, they may be useful for predicting disease onset. Whether autoantibody tests can be used in this way depends on their sensitivity, specificity, and positive predictive value. (Source)

Sensitivity of Prediction

This is the ratio of people with a particular autoantibody who develop an associated disease, compared to the total number of people who develop the disease. If every person who develops a specific autoimmune disease has that autoantibody, this indicates a high disease sensitivity. If you are found to carry an autoantibody with high sensitivity of prediction, it helps you know how likely you are to develop an autoimmune disorder. Having this information may give you time to take measures to avoid disease onset, or to minimize your symptoms if you do develop the disorder.

Specificity of Prediction

This is the ratio of people without a particular autoantibody who do not develop an associated disease, compared to the total number of people who do not develop that disease. It is useful for predicting the chances that an individual will not have a disease associated with that antibody.

Positive Predictive Value

This is the ratio of people who test positive through autoantibody testing and who develop clinical disease, compared to the overall number of people who tested positive through the autoantibody testing, whether they developed clinical disease or not. A high positive predictive value indicates that more people with the autoantibody but without the clinical disease will eventually develop the disease. 

Autoantibody Tests

Because healthy people may have some circulating autoantibodies, the presence of autoantibodies in itself doesn’t ensure a diagnosis of autoimmune disease. Often, multiple laboratory tests combined with evaluation of signs and symptoms are needed in order to reach a diagnosis. Components of a laboratory exam may include a blood count with a metabolic panel for different blood components, inflammatory markers, and autoantibodies. (Source)

Autoantibody testing is usually done using the enzyme-linked immunosorbent assay (ELISA) method. With ELISA, laboratory plates coated with specific antigens are exposed to the patient’s serum (the liquid part of the blood left when red blood cells and platelets are removed). If antibodies to the antigens are present, they will bind with the antigens. (Source) 

An Introduction to Common Autoantibodies

Research into autoantibodies and their relation to autoimmune disease is ongoing, but the following are some of the most common and best-understood autoantibodies.

Antinuclear Antibodies

Most autoantibodies bind to the surface of cells, but antinuclear antibodies (ANAs) bind to components of a cell’s nucleus, or to other substances inside the cell. Antinuclear antibodies are associated with a number of autoimmune diseases but may also be detected in healthy people. Testing for them is helpful in ruling a diagnosis in or out, but they can’t be used by themselves to confirm a diagnosis. (Source)

Extractable Nuclear Antigen (ENA) Antibodies

A subset of ANAs are known as extractable nuclear antigen antibodies (ENAs), which react with specific proteins in the cell nucleus. A positive ANA result may be followed by testing for ENAs to help narrow down an autoimmune disease diagnosis. (Source, Source)

Anti-Smith (Anti-Sm) Antibodies

Anti-Smith antibodies are specific for systemic lupus erythematosus (SLE) and important for its classification. The level of antibodies present in blood serum is correlated with disease activity of SLE. Thus, these antibodies are clinically important as a marker for disease activity and associated disease flares. (Source, Source)

Anti-RNP Antibodies 

Anti-RNP (ribonucleoprotein) antibodies may be detected in the presence of several connective tissue diseases, and high levels of anti-RNP antibodies are associated with a diagnosis of mixed connective tissue disease (MCTD, a rare autoimmune condition with symptoms of three different diseases). (Source, Source)

SS-A and SS-B Antibodies

Autoantibodies to the antigens Ro (SS-A) and La (SS-B) are associated especially with Sjögren’s syndrome and SLE, but may be present in many other autoimmune diseases. In pregnant women, these antibodies indicate an increased risk of neonatal lupus syndrome, which is severe and is associated with congenital heart block. (Source, Source, Source)

Anticardiolipin Antibody

Anticardiolipin antibody (ACA) targets platelets and cell membranes made up of phospholipids. It is implicated in SLE, rheumatoid arthritis, and a condition called antiphospholipid syndrome (APS), which leads to blood clots and increased risk of premature birth and fetal loss. (Source, Source)

Rheumatoid Factors (RF)

The antibodies known as rheumatoid factors are sometimes found in healthy people, and it’s believed they have a protective function. In some cases, though, it is believed they may mutate into pathogenic forms that can cause not just rheumatoid arthritis, but other autoimmune and non-autoimmune diseases as well. (Source, Source)

Thyroid Antibodies

Thyroid disorders such as Hashimoto’s thyroiditis, which causes hypothyroidism, and Graves’ disease, which causes hyperthyroidism, are autoimmune diseases. They are associated with antibodies to an enzyme called thyroid peroxidase (TPO) and to a protein called thyroglobulin (Tg). (Source, Source)

Diabetes Autoantibodies

Destruction of insulin-producing cells in the pancreas leads to type 1 diabetes. Antibodies that bind to the autoantigens glutamic acid decarboxylase, IA-2, and insulin have been identified. Studies show that the presence of two or more of these autoantibodies makes development of type 1 diabetes more likely than does presence of a single autoantibody. (Source, Source)

Gliadin Antibodies

Celiac disease is associated with antibodies to gliadin, a component of gluten, which is found in wheat, barley, rye, and triticale (a cross between wheat and rye). Currently, avoiding gluten in the diet is the treatment of choice for celiac disease. To test for gliadin antibodies, though, the patient must ingest gluten so that antibodies are activated and available for testing. (Source, Source)

Adrenalitis-Associated Antibodies

Adrenalitis is an autoimmune disease that affects the adrenal glands, which are located on top of the kidneys and produce hormones, including cortisol, that are critical to life. Destruction of the adrenal glands leads to a condition of adrenal insufficiency known as Addison’s disease. The development of adrenal failure is more likely when the antibodies are present in childhood. (Source, Source)

What’s the Treatment for Autoantibodies?

Research continues into treating autoimmune diseases by removing pathogenic autoantibodies from the body. Methods include engineering T cells to attack B cells that carry specific autoantibodies, or removing blood from the body, cleansing it of autoantibodies, and returning it to circulation (somewhat similar to hemodialysis). (Source, Source)

Rather than targeting specific autoantibodies, treatments often focus on immunosuppression, or limiting immune reactions in general. Some drugs, for example, slow down replication of the B cells that produce antibodies. Immunosuppression increases susceptibility to infection and so carries its own risks. (Source)

The Bottom Line

Even healthy people may have some circulating autoantibodies, but genetic predisposition or environmental or other triggers may lead to development of autoimmune disorders. There is currently no cure for autoimmune disease, but it may be possible to suppress production of some autoantibodies. Testing for autoantibodies may help predict the onset of autoimmune disease, diagnose and monitor progression, and help guide treatment. Promising research suggests it may be possible to treat autoimmune diseases by removing autoantibodies from the body.

Making sense of all the terminology, diagnostic tools, and treatments for autoimmune conditions can be overwhelming. If you’re looking for additional education and support in managing your autoimmune symptoms, the experts at WellTheory are here to help. The WellTheory care team can develop a personalized care plan while also providing expert-led masterclasses and office hours to help decipher all the complexities of living with an autoimmune condition.