Most Common Systemic Autoimmune Disorders
Definition and Principle of Antinuclear Antibody Testing
Types of Antinuclear Antibodies
Types of Antinuclear Immunofluorescent Patterns
– Including Color Pictures of Each
Patterns of Immunofluorescence Associated with Autoantibodies and Autoimmune Diseases
Confirmatory Autoantibody Testing Related to ANA Patterns and Autoimmune Diseases
Etiology of Systemic Lupus Erythematosus
Etiology of Rheumatoid Arthritis
Most Common Organ Specific Autoimmune Diseases
Autoantibodies Related to Each Organ Specific Autoimmune Disease

Etiology of Autoimmune Disorders

Generally speaking, an autoimmune diseases are conditions in which your immune system mistakenly attacks the cells and organs within your own body. Typically, the immune system will guard against germs like bacteria and viruses, and will know the difference between your cells and the foreign cells. When it senses these foreign invaders, it sends out fighter cells to attack them. With autoimmune diseases, the immune system mistakes part of your body, like your joints or skin, or even your organs as foreign, therefore it releases proteins called autoantibodies that end up attacking healthy cells. Some autoimmune diseases target only one organ, such as type 1 diabetes which damages the pancreas. Other diseases, like systemic lupus erythematosus (SLE), will often affect the entire body. Even today, doctors are not entirely certain as to what causes the immune-system misfires. And yet, some people are more likely to get an autoimmune disease than others.

Certain autoimmune diseases, like multiple sclerosis and lupus, tend to run in families. Though, not every family member will necessarily have the disease, but they may inherit a susceptibility to it. Some autoimmune diseases are more common in certain ethnic groups. For example, lupus affects more African-American and Hispanic people than Caucasians. According to a 2014 study done by Scott M. Hayter and Matthew C. Cook in Autoimmunity Reviews by Elsevier, women get autoimmune diseases at a rate of about 2 to 1 compared to men — 6.4 percent of women vs. 2.7 percent of men. Often the disease starts during a woman’s childbearing years (ages 15 to 44). Due to the number of incidence of autoimmune diseases rising, researchers suspect environmental factors like infections and exposure to chemicals or solvents might also be responsible.

Most Common Systemic Autoimmune Disorders

The ten most common autoimmune disorders, not listed by number of occurrences, are:

1) Type 1 Diabetes
The pancreas produces the hormone insulin, which helps regulate blood sugar levels. In type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the pancreas.

2) Rheumatoid Arthritis (RA)
In rheumatoid arthritis (RA), the immune system attacks the joints.

3) Psoriasis/Psoriatic Arthritis
Skin cells normally grow, then shed when they’re no longer needed. Psoriasis causes skin cells to multiply too quickly, and extra cells will build up and form inflamed red patches, commonly with silver-white scales of plaque on the skin.

4) Multiple Sclerosis
Multiple sclerosis (MS) damages the myelin sheath, the protective coating that surrounds nerve cells, in your central nervous system. Damage to the myelin sheath slows the transmission speed of messages between your brain and spinal cord to and from the rest of your body.

5) Systemic Lupus Erythematosus (SLE)
Doctors in the 1800s first described lupus as a skin disease because of the rash it commonly produces. However, the systemic form, which is most the common, actually affects many organs, including the joints, kidneys, brain, and heart.

6) Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a term used to describe conditions that cause inflammation in the lining of the intestinal wall. Each type of IBD affects a different part of the GI tract, with Crohn’s Disease affecting any part of the digestive track from mouth to anus; and Ulcerative Colitis only affecting the large intestine and rectum.

7) Addison’s Disease
Addison’s disease affects the adrenal glands, which produce the hormones cortisol and aldosterone as well as androgen hormones.

8) Graves’ Disease
Graves’ disease attacks the thyroid gland in the neck, causing it to produce too much of its hormones. Thyroid hormones control the body’s energy usage, known as metabolism.

9) Celiac disease
People with celiac disease can’t eat foods containing gluten, a protein found in wheat, rye, and other grain products. When gluten is in the small intestine, the immune system attacks this part of the gastrointestinal tract and causes inflammation.

10) Myasthenia Gravis
Myasthenia gravis affects nerve impulses that help the brain control the muscles. When the communication from nerves to muscles is impaired, signals can’t direct the muscles to contract.

Definition and Principle of Antinuclear Antibody Testing

This testing is used as one of the tests to diagnose Systemic Lupus Erythematosus (SLE). The antinuclear antibody panel is a blood test that looks at antinuclear antibodies (ANA). ANA are antibodies produced by the immune system that bind to the body’s own tissues. The antinuclear antibody test looks for antibodies that bind to a part of the cell called the nucleus. The screening test determines whether such antibodies are present, and the test also measures the level (called the titer) and the pattern, which can be helpful. If the test is positive, a panel of tests may be done to identify specific antigen targets.

The principle is an agglutination test. When the test serum (containing antinuclear antibodies) is brought into contact with latex particles coated with DNP (Deoxyribo nucleoprotein), agglutination of the latex particles takes place indicating a positive reaction.

Types of Antinuclear Antibodies

There are many subtypes of ANAs such as anti-Ro antibodies, anti-La antibodies, anti-Sm antibodies, anti-nRNP antibodies, anti-Scl-70 antibodies, anti-dsDNA antibodies, anti-histone antibodies, antibodies to nuclear pore complexes, anti-centromere antibodies and anti-sp100 antibodies. Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus.

Types of Antinuclear Immunofluorescent Patterns

Homogeneous (diffuse) pattern (the whole nucleus stains green – B in photo below): found with antibodies to chromatin, histones, and (occasionally) double stranded DNA. This pattern is seen in lupus and occasionally in other autoimmune diseases.

Speckled pattern (random speckles all over the nucleus – (E in photo below): found with antibodies to non-DNA nuclear antigens (like ribonucleoprotein). This is the most common immunofluorescent pattern overall – and the least specific for any particular autoimmune disease.

Nucleolar pattern (a few spots of green within the nucleus – C in photo below): found with antibodies to RNA. Found most frequently in patients with systemic sclerosis (a different autoimmune disease)

Rim or peripheral pattern (green around the periphery of the nucleus – D in photo below): found with antibodies to double-stranded DNA. This pattern is seen frequently in lupus.


Confirmatory Autoantibody Testing Related to ANA Patterns and Autoimmune Diseases

The American College of Rheumatology states that the sensitivity and simplicity of an ANA test makes it extremely popular initial test to evaluate for lupus in particular. Since most people (more than 95% of individuals) with lupus will test positive, a negative ANA test can be helpful in excluding that diagnosis. That said, only about 11 – 13% of persons with a positive ANA test have lupus and up to 15% of completely healthy people have a positive ANA test. Thus a positive ANA test does not automatically translate into a diagnosis of lupus or any autoimmune or connective tissue disease. A negative ANA reading means no autoantibodies are present in the body. However, a positive ANA reading alone does not indicate an autoimmune disease. The prevalence of ANAs in healthy individuals is about 3 – 15%. The production of these autoantibodies is strongly age-dependent, and increases to 10 – 37% in healthy persons over the age of 65. Even healthy people with viral infections can have a positive ANA, albeit for a short time. Some medications can cause a positive ANA. Other conditions, such as cancer, can cause a positive ANA. To make a definite diagnosis, your doctor will need more blood tests along with history of your symptoms and a physical examination.

Etiology of Systemic Lupus Erythematosus

The cause of SLE is not clear. It is thought to involve genetics together with environmental factors. Among identical twins, if one is affected there is a 24% chance the other one will be as well. Female sex hormones, sunlight, smoking, vitamin D deficiency, and certain infections, are also believed to increase the risk. There are a number of other kinds of lupus erythematosus including discoid lupus erythematosus, neonatal lupus, and subacute cutaneous lupus erythematosus. Rate of SLE varies between countries from 20 to 70 per 100,000. Women of childbearing age are affected about nine times more often than men. While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected. Those of African, Caribbean, and Chinese descent are at higher risk than white people.

Etiology of Rheumatoid Arthritis

While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body’s immune system attacking the joints. This results in inflammation and thickening of the joint capsule, and it also affects the underlying bone and cartilage. Other diseases that may present similarly include systemic lupus erythematosus, psoriatic arthritis, and fibromyalgia among others.

Most Common Organ Specific Autoimmune Diseases

Autoimmune Hepatitis
Autoimmune hepatitis is a chronic autoimmune disorder that affects the liver. The liver becomes inflamed when the body’s immune cells wrongly identify liver cells as foreign invaders. Autoimmune hepatitis is sometimes referred to as chronic active hepatitis (CAH), but autoimmunity is not its only cause. Allergic reactions to medications, excessive alcohol use, and viruses also can cause it. Autoimmune hepatitis is differentiated from these other forms of chronic hepatitis by the presence of auto-antibody markers.

Hashimoto’s Thyroiditis
Hashimoto’s thyroiditis, also referred to as chronic lymphocytic thyroiditis or autoimmune thyroiditis, is caused by an autoimmune reaction to proteins in the thyroid gland. This inappropriate reaction causes the thyroid gland to swell, which reduces its function.

Grave’s Disease
Like Hashimoto’s disease, Graves’ is an autoimmune disorder that disturbs the thyroid — but with the opposite effect. Graves’ causes the thyroid to over function, leading to a series of symptoms, many of which are in contrast to those caused by Hashimoto’s. Graves’ disease causes an increase in production of thyroid hormone, which helps regulate metabolism. The hyper functioning thyroid caused by Graves’ leads to an increase in metabolism.

Type 1 Diabetes
Sometimes referred to as insulin-dependent diabetes or juvenile diabetes, type 1 diabetes occurs when a person’s body produces little or no insulin. Insulin is a necessary hormone because it’s what allows sugar to enter the cells. When sugar can’t enter the cells, the body can’t get energy, so type 1 diabetes patients often experience increased hunger — yet tend not to gain weight.

Addison’s Disease
This condition occurs when the adrenal glands, small organs that sit on top of the kidneys, don’t produce enough hormones. Specifically, Addison’s patients don’t produce enough cortisol and aldosterone, two hormones that are produced in the outer portion (the cortex) of the adrenal glands. This is why the disorder is sometimes referred to as adrenal insufficiency.

Sjogren’s Syndrome
This autoimmune condition attacks the glands that produce tears and saliva. As a result, people who have Sjögren’s syndrome experience dry eyes and mouth. In most cases of Sjogren’s, symptoms are limited to the tear ducts and salivary glands, but in severe cases, the condition also can affect the kidneys and lungs.

Autoantibodies Related to Each Organ Specific Autoimmune Disease

1) Anti-dsDNA: Systemic lupus erythematosus (SLE)
2) Anti-histone antibodies: SLE and drug-induced lupus erythematosus (LE)
3) Anti-La/SS-B autoantibodies: Primary Sjögren syndrome
4) Anti-RNP: Mixed connective-tissue disease, SLE
5) Anti-Ro/SS-A autoantibodies: Systemic lupus erythematosus (SLE), primary Sjögren syndrome, neonatal heart block
6) Anti-CCP: Rheumatoid arthritis
7) Anti-smooth muscle antibody: Chronic autoimmune hepatitis
8) Anti-thyroid autoantibodies: Hashimoto thyroiditis, Graves disease
9) Anti-transglutaminase antibodies: Celiac disease, dermatitis herpetiformis
10) Liver kidney microsomal type 1 antibody: Autoimmune hepatitis
11) Lupus anticoagulant: SLE
12) Rheumatoid factor: Rheumatoid arthritis