I. Introduction

A positive ANA is often seen in people with systemic lupus erythematosus, Sjogren’s syndrome, and rheumatoid arthritis. According to the Lupus Foundation of America, as many as 1.5 million Americans have some type of lupus. The American College of Rheumatology reports that anywhere from 400,000 to 3.1 million adults have Sjogren’s syndrome. Dr. Jennifer Freeman of the Rheumatoid Arthritis Support Network states that more than 1.3 million Americans have rheumatoid arthritis.

This guide provides detailed information about the antinuclear antibody test, including why it’s necessary, when the test should be performed, and what the results mean. It also provides an overview of three conditions associated with a positive ANA: systemic lupus erythematosus, Sjogren’s syndrome, and rheumatoid arthritis.

II. Overview of the Antinuclear Antibody Test

Why should I get tested?

The purpose of the ANA test is to check for the presence of antinuclear antibodies in the blood. Health care providers often order this test for people who have fevers with no obvious cause, muscle pain, joint pain, joint swelling, and fatigue. The test may also be ordered for an individual who develops a red, butterfly-shaped rash, called a malar rash, on the face.

When should I get tested?

An ANA test is indicated when an individual has signs or symptoms of an autoimmune disorder that can’t be explained by another diagnosis. For example, someone with a fever of unknown origin should have the ANA test as soon as a health care provider feels it’s appropriate. The American Academy of Family Physicians defines a fever of unknown origin as a fever above 100.9 degrees Fahrenheit that lasts for more than three weeks and is not caused by an infection or any other obvious cause.

What is required for the test?

The ANA test requires a small sample of blood.

What do I need to do to prepare for the test?

No special preparation is needed for the ANA test.

III. The Basics of Systemic Lupus Erythematosus, Sjogren's Syndrome, and Rheumatoid Arthritis

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is one of several types of lupus that primarily afflicts women, but can also affect men and even children. In individuals with lupus, the immune system can’t distinguish antigens from healthy cells, causing the immune system to attack the organs and other tissues. Researchers do not yet know what causes SLE, but it may be related to gene mutations, exposure to harmful chemicals, or the use of certain medications. Since lupus is much more common in women, some researchers believe hormones play a role in the development of SLE.

SLE causes a variety of symptoms, including fatigue, muscle pain, fevers of unknown origin, hair loss, increased sensitivity to sunlight, swollen glands, muscle pain, joint pain, and a butterfly-shaped rash on the face. Depending on which tissues are involved, SLE may also cause symptoms specific to one or two organs. For example, lupus can damage the heart, leading to inflammation of the heart muscle and increasing the risk for high blood pressure and other heart-related complications.

Sjogren's Syndrome

Like lupus, Sjogren’s syndrome is an autoimmune disorder in which the immune system can’t tell the difference between healthy cells and foreign invaders like bacteria and viruses. As a result, the immune system attacks the tear ducts and salivary glands, causing dry eyes and a dry mouth. Sjogren’s syndrome can also cause joint pain, kidney damage, burning and tingling sensations, clumsiness, and weakness. Women develop Sjogren’s syndrome more often than men.

Rheumatoid Arthritis

Many people develop osteoarthritis as they grow older, causing joint pain and stiffness, but rheumatoid arthritis (RA) is something different. In people with RA, the immune system attacks the joints, causing pain, stiffness, swelling, and limited mobility. RA is common in the wrists and fingers, but it may affect any of the joints in the body. In some people, RA also affects the lungs, mouth, and eyes, causing symptoms such as eye pain, chronic cough, scarring of the lungs, and difficulty opening the mouth. Researchers don’t know what causes rheumatoid arthritis, but the condition may be linked to hormones, environmental conditions, or genetic factors.

IV. How the ANA Test Works

Laboratory personnel use three primary methods to detect the presence of antinuclear antibodies in blood samples: indirect immunofluorescence (IIF), multiplex immunoassay (MIA), and enzyme immunoassay (EIA). With IIF, the patient’s blood sample is incubated with a prepared tissue sample. Once the slides are washed, they’re incubated with antibodies that have been treated with a special dye. If antinuclear antibodies are present, the fluorescent dye makes them visible under a microscope. After viewing the slides, a laboratory scientist notes the pattern of fluorescence as well as the intensity of the fluorescence, which can provide important clues as to the cause of the patient’s symptoms.

The MIA method uses polystyrene beads combined with known ANA antigens. After creating a bead “cocktail,” a scientist adds the blood sample and waits to see if any of the patient’s antibodies bind with any of the beads. With the EIA method, a scientist makes an antigen mixture and applies it to a solid surface. Fluorescent antibodies are used to detect the presence of antinuclear antibodies in the patient’s blood sample.

If the ANA test is positive, laboratory personnel perform a titer test to determine the amount of antinuclear antibodies present. During this procedure, a scientist keeps diluting the sample until no antinuclear antibodies can be detected. The higher the titer, the more antinuclear antibodies in the blood. A titer is expressed as a ratio, such as 1:40 or 1:320.

V. Treatments for Systemic Lupus Erythematosus, Sjogren's Syndrome, and Rheumatoid Arthritis

Systemic lupus, Sjogren’s syndrome, and rheumatoid arthritis can’t be cured. Therefore, the aim of treatment is to stop each condition from growing worse and prevent additional damage to healthy tissues. It’s important to see a rheumatologist — a doctor who specializes in autoimmune disorders and musculoskeletal diseases — to identify an appropriate treatment plan. Not everyone with each condition has the same symptoms or the same level of disease progression, so ongoing monitoring is essential.

Systemic Lupus Erythematosus

Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually one of the first treatments prescribed for individuals with lupus. Although NSAIDs have side effects, they’re typically less severe than the ones produced by steroids, immunosuppressants, and other lupus treatments. NSAIDs help people with lupus by reducing inflammation, which can relieve lupus-related pain. Steroids also relieve inflammation, reducing swelling, tenderness, and pain. The steroids used to treat lupus are not the same as the steroids used to enhance athletic performance. Steroids can cause serious side effects, so they’re usually only taken when an individual is having an active lupus flare.

Medications used to treat malaria, known as antimalarials, are also used to relieve the symptoms of lupus. Unlike steroids, antimalarials are often prescribed for long-term use. They can stop lupus from progressing and control pain, swelling, and other symptoms. The hormone DHEA is sometimes prescribed to control the symptoms of mild or moderate lupus. This hormone helps with hair loss, fatigue, joint pain, memory loss, and difficulty thinking clearly. Immunosuppressants weaken the immune system so that it can’t do as much damage to healthy tissues. These medications are effective for treating lupus, but people who take them have a high risk of catching infections because their weakened immune systems aren’t as effective at fighting off bacteria, viruses, and other organisms.

Sjogren's Syndrome

To relieve dry mouth, people with Sjogren’s syndrome should drink plenty of water, chew sugar-free gum, or suck on sugar-free candy. If these lifestyle adjustments aren’t effective, medications are available to increase the amount of saliva produced by the salivary glands. Some people with Sjogren’s syndrome experience vaginal dryness, dry skin, dry lips, and dryness of the nose. Vaginal dryness can be alleviated with vitamin E oil, vaginal lubricants, estrogen cream, and other products created to increase vaginal moisture. Lotion is helpful for dry skin, especially when applied right after showering or bathing. Lip balms and petroleum-based lip products can prevent cracking and ease the discomfort of dry lips. If the inside of the nose is dry, over-the-counter nasal sprays can add moisture and relieve discomfort.

Since a lack of saliva increases the risk for acid reflux, some people with Sjogren’s syndrome take antacids or modify their diets to avoid spicy foods and other reflux triggers. Several medications are available to treat joint pain caused by Sjogren’s syndrome, including NSAIDs, steroids, and disease-modifying anti-rheumatic drugs (DMARDs) that block inflammation, relieving pain and reducing stiffness in the joints.

Rheumatoid Arthritis

Some of the same medications used to treat lupus and Sjogren’s syndrome can also treat rheumatoid arthritis. For example, NSAIDs and steroids are used to control inflammation. DMARDs can slow the progression of RA and prevent additional joint damage. Biologics and JAK inhibitors are two subcategories of DMARDs that can help people with RA relieve discomfort and prevent additional joint damage. Biologics target specific components of the immune response, slowing down or even stopping the progression of RA. JAK inhibitors target a specific pathway of the immune response, which can also slow the course of the disease.

In people who have permanent joint damage due to RA, joint-replacement surgery may also be an option. During this surgery, a damaged joint is replaced with an artificial joint, restoring lost function and improving the patient’s mobility. Knee and hip replacements are the most common, but other damaged joints can also be replaced.

VI. FAQs

If my ANA is positive, do I definitely have an autoimmune disorder?

No. Some people have low levels of antinuclear antibodies even if they don’t have any autoimmune disorders. If an individual has a low ANA titer, the risk of developing an autoimmune disorder is lower than it is in people who have a very high ANA titer.

If my ANA is negative, does that mean I definitely don't have an autoimmune disorder?

No. Although a negative ANA makes it less likely that an individual has an autoimmune disorder, it’s possible to have a disorder like rheumatoid arthritis without having a positive ANA. This is why it’s so important to be monitored by a medical professional. Even if the ANA test is negative, an individual could have other antibodies causing symptoms such as pain and fatigue.

My lab report mentions an ANA pattern. What does this mean?

Positive ANA tests produce several different patterns of fluorescence. Although the pattern isn’t used to make a definitive diagnosis, it can help health care providers determine the best course of action for patients with positive ANA results. A diffuse pattern is associated with systemic lupus erythematosus, while a nucleolar pattern is often found in people with scleroderma, an autoimmune disorder that causes the skin to harden. The speckled pattern and peripheral pattern are also associated with lupus.

If my ANA is positive, do I need additional tests?

In most cases, a positive ANA indicates the need for additional testing. The tests ordered depend on how high the ANA titer is and what symptoms the individual is experiencing. Anti-dsDNA testing may be done to determine if the individual has antibodies that target double-stranded DNA, which is the genetic material found in the nucleus of each cell. A high anti-dsDNA level is associated with lupus. If a medical professional suspects that a patient has rheumatoid arthritis, the rheumatoid factor test can be used to determine if RF antibodies are present in the patient’s blood. Anti-Rho and anti-La testing are used in the diagnosis of Sjogren’s syndrome.

What other conditions can cause a positive ANA test?

Certain infections, such as HIV, hepatitis, and the Epstein-Barr virus, can cause a positive ANA result. A positive ANA has also been associated with scleroderma, lymphoma, autoimmune hepatitis, mixed connective tissue disease, thyroid disease, and myositis, a disease that causes inflammation of the muscles.

VII. Additional Resources

To learn more about systemic lupus erythematosus, Sjogren’s syndrome, and rheumatoid arthritis, plus testing for these conditions, visit the following resources.

NameWebSummary
Lupus Foundation of Americawww.lupus.org/resources/what-is-lupusThe Lupus Foundation of America explains what lupus is, provides information about each type of lupus, and describes the risk factors for developing this autoimmune disorder.
Sjogren’s Syndrome Foundationwww.sjogrens.org/home/about-sjogrensThe Sjogren’s Syndrome Foundation provides an overview of Sjogren’s syndrome and links to a video aimed at helping newly diagnosed patients learn more about the disorder.
Arthritis Foundationwww.arthritis.org/about-arthritis/types/rheumatoid-arthritis/The Arthritis Foundation gives an introduction to rheumatoid arthritis, including the symptoms and treatment options.
Johns Hopkins Lupus Centerwww.hopkinslupus.org/lupus-tests/lupus-blood-tests/Learn more about the blood tests used to diagnose lupus with this guide from the Johns Hopkins Lupus Center.
Johns Hopkins Medicinewww.hopkinsmedicine.orgFind out about the tests used in the diagnosis and management of Sjogren’s syndrome.

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