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Changes in ANA Patterns: Why They Occur With Lupus

Medically reviewed by Neil J. Gonter, M.D.
Written by Bora Lee, Ph.D.
Posted on June 29, 2023

Have you been experiencing stiffness and swelling in your joints? Or a rash on your face that you haven’t noticed before? Have you wondered how to figure out if these symptoms are caused by lupus?

Typically, the first step in finding out whether you have lupus is for your doctor to order an antinuclear antibody (ANA) test. An antinuclear antibody test is a blood test that can help diagnose and monitor the progression of lupus. But sometimes, the results can be confusing.

A MyLupusTeam member shared this sentiment: “I’ve had two ANA tests in the last month and they are showing different results. I don’t know what to make of this!” Learn more about what the results of your ANA test mean and why they may change.

What Are Autoantibodies?

Lupus is an autoimmune disease in which a person’s immune system attacks their own cells and tissues. Normally, the immune system makes antibodies — proteins that bind to foreign organisms like bacteria or viruses — to get rid of them. The most common type of lupus is systemic lupus erythematosus (SLE).

In autoimmune diseases such as SLE, the immune system mistakenly considers its own tissues as foreign and produces antibodies against them. These antibodies are called autoantibodies. When autoantibodies accumulate in the body, it leads to inflammation and organ damage often seen in people with SLE.

Antinuclear Antibodies

According to Johns Hopkins Lupus Center, about 98 percent of people with SLE have ANAs in their blood. ANAs recognize components of the nuclei in your cells. Nuclei are structures in the cell that contain genetic material. The presence of ANAs in the majority of people with SLE makes them a useful tool for diagnosing SLE.

If you have symptoms of SLE or other autoimmune diseases, your doctor will order an ANA test to check for the presence and levels of ANAs in your blood. For an ANA test, you will have a sample of blood taken, and the results will be interpreted by health care professionals.

The results of a positive ANA test consist of two parts — the titer and the staining pattern. The titer shows the level of ANAs in the sample. It’s reported as a ratio. Generally, a ratio of 1:80 is considered to be a positive ANA sample. Titers higher than 1:160 are found in people with active SLE.

The pattern refers to how the ANA sample is detected visually, using different kinds of staining techniques:

  • Homogeneous — Staining is even in the entire nucleus and is commonly found in people with SLE and discoid lupus erythematosus (DLE).
  • Peripheral — Staining is seen at the edges of the nucleus and is found in those with SLE and calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome.
  • Speckled — Staining is seen as small dots in the nucleus and is found in people with SLE, mixed connective tissue disease (MCTD), scleroderma, and Sjögren’s syndrome (an autoimmune disease that causes dry eyes and dry mouth).
  • Nucleolar — Staining is seen in the nucleolus within the nucleus and is found in those with scleroderma.
  • Centromere — Staining is on the centromeres of chromosomes and is found in people with scleroderma and CREST syndrome.

Changes in ANA Test Results

If you have lupus, there are several reasons why your ANA test results may change over time. They may change if you have multiple autoimmune conditions, if your lupus gets more severe, if you’re experiencing a flare, or if you’re undergoing treatment.

Multiple Autoimmune Conditions

ANAs are also present when people have other autoimmune diseases, including rheumatoid arthritis, Sjögren’s syndrome, and scleroderma. Many people with SLE have one or several of these other conditions, so their ANA test results may show mixed patterns. One member of MyLupusTeam shared, “When I was told I had lupus five months ago, I was told that I have eight other patterns from the autoimmune spectrum.”

Lupus Severity

Certain ANA patterns are found at a higher rate in people with more severe lupus. Researchers have found that peripheral, speckled, and mixed staining ANA patterns in individuals with SLE may have a higher likelihood of being associated with severe disease and organ damage. Specific ANA patterns are associated with higher levels of proteins that become activated in active SLE.

Active Lupus and Treatment

The patterns of ANAs have also been shown to change over time, depending on whether you’re in a lupus flare and whether you’re undergoing treatment. For example, a person with active disease or a flare may have a peripheral, speckled, or mixed pattern of the two. As they undergo treatment with steroids or other immunosuppressants, their ANA pattern may become homogeneous. It’s important to note that a homogeneous ANA pattern does not necessarily mean there is disease activity or flare-up in lupus. The ANA pattern by itself cannot be relied on to determine how active the disease is — it needs to be compared with clinical symptoms, physical exam results, and other lab tests to see if they match or are related.

Your rheumatologist can give you more information about what may be affecting your ANA test results based on your demographics, medical history, and any treatments you’ve had.

Limitations of the ANA Test

While the ANA test provides valuable information about the levels and locations of ANAs, it has limitations for use in the diagnosis of SLE:

  • Up to 30 percent of people with SLE test negative for ANAs.
  • Up to 10 percent of healthy individuals and 20 percent of healthy women test positive for ANAs.
  • Many people with other autoimmune diseases, such as scleroderma, rheumatoid arthritis, or Sjögren’s syndrome, also test positive for ANAs.

Antinuclear Antibody Panel

The results of the ANA test shouldn’t be used alone to diagnose SLE. They need to be verified by additional testing to make an accurate SLE diagnosis. If you test positive for ANAs, your doctor will order an ANA panel to confirm a lupus diagnosis.

An ANA panel checks for different types of autoantibodies (described below) in your blood sample.

Anti-Double-Stranded DNA Antibodies

Found in 68 percent to 83 percent of people with SLE, anti-double-stranded DNA (anti-dsDNA) antibodies are found at high levels in people with SLE. High anti-dsDNA levels can signal active SLE and even predict flares.

The levels of anti-dsDNA antibodies can change drastically over time, depending on lupus disease activity and treatment. Anti-dsDNA antibody levels can rise during a flare and almost disappear during treatment with steroids or other immunosuppressive drugs.

Anti-Smith Antibodies

Anti-Smith (anti-Sm) antibodies are found in 5 percent to 30 percent of those with SLE. They are found almost exclusively in people with SLE, so their presence can help confirm an SLE diagnosis.

Anti-U1 Ribonucleoprotein Antibodies

As cited in the journal Autoimmunity, although found in about 25 percent to 47 percent of people with SLE, anti-U1 ribonucleoprotein (anti-RNP) antibodies are not only found in SLE. They are also found in people with mixed connective tissue disease (MCTD), a disease with a combination of symptoms of SLE, rheumatoid arthritis, and scleroderma. Therefore, the presence of anti-RNP antibodies and ANAs can’t confirm a lupus diagnosis.

Anti-Ro and Anti-La Antibodies

Anti-Ro antibodies are found in 40 percent to 90 percent of people with SLE, and anti-La antibodies are found in about 45 percent of people with SLE. They are also found in those with other autoimmune disorders, including Sjögren’s syndrome, subacute cutaneous lupus erythematosus (SCLE), and neonatal lupus erythematosus (NLE) — affecting infants of pregnant women with lupus.

Testing ANA Levels Over Time

ANA levels may change with disease activity, but they cannot be relied on to determine the level of disease activity. There is no definite connection between ANA levels and disease activity, and repeating the measurements does not provide useful information for assessing disease activity.

The use of ANA tests in diagnosing lupus has been controversial because of the high false-positive rate, which means that people may be incorrectly diagnosed with this condition. Doctors and health care professionals may interpret results differently, which can lead to variations in their understanding.

However, when used in combination with other clinical tests, especially with anti-dsDNA and anti-Smith antibody tests, the results of ANA tests can be very helpful for diagnosing SLE. If you have questions on how to interpret your ANA test results, ask your doctor to go over them with you.

Talk With Others Who Understand

MyLupusTeam is the social network for people with lupus and their loved ones. On MyLupusTeam, more than 223,000 members come together to ask questions, give advice, and share their stories with others who understand life with lupus.

Have you had antinuclear antibody test results that changed over time? Share your experience in the comments below, or start a conversation by posting on MyLupusTeam.

References
  1. High Titers of Antinuclear Antibody and the Presence of Multiple Autoantibodies Are Highly Suggestive of Systemic Lupus Erythematosus — Scientific Reports
  2. Lupus — MedlinePlus
  3. Immunity Types — Centers for Disease Control and Prevention
  4. Definition of Autoimmunity & Autoimmune Disease — Johns Hopkins Medicine Pathology
  5. An Update on Autoantibodies in Systemic Lupus Erythematosus — Current Opinions in Rheumatology
  6. Lupus Blood Tests — Johns Hopkins Lupus Center
  7. Antinuclear Antibody Panel — Mount Sinai
  8. New Insights Into the Role of Antinuclear Antibodies in Systemic Lupus Erythematosus — Nature Reviews Rheumatology
  9. Antinuclear Antibodies (ANA) — University of Florida Pathology Laboratories
  10. Clinical Relevance of HEp-2 Indirect Immunofluorescent Patterns: The International Consensus on ANA Patterns (ICAP) Perspective — Annals of the Rheumatic Diseases
  11. Antinuclear Antibodies: When To Test and How To Interpret Findings — The Journal of Family Practice
  12. Antinuclear Antibody Testing for the Diagnosis of Systemic Lupus Erythematosus — Medical Clinics of North America
  13. Patients With Overlap Autoimmune Disease Differ From Those With ‘Pure’ Disease — Lupus Science & Medicine
  14. Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters — Frontiers in Immunology
  15. Flares in Systemic Lupus Erythematosus: Diagnosis, Risk Factors and Preventive Strategies — Mediterranean Journal of Rheumatology
  16. Biomarkers as Entry Criteria for Clinical Trials of New Therapies for Systemic Lupus Erythematosus — Arthritis & Rheumatology
  17. Lupus Blood Test Results Explained — Hospital for Special Surgery
  18. Autoantibody-Dependent Amplification of Inflammation in SLE — Cell Death & Disease
  19. A Surge in Anti-dsDNA Titer Predicts a Severe Lupus Flare Within Six Months — Lupus
  20. Anti-Sm Antibodies in the Classification Criteria of Systemic Lupus Erythematosus — Journal of Translational Autoimmunity
  21. Anti-Sm and Anti-RNP Antibodies — Autoimmunity
  22. Clinical and Pathological Roles of Ro/SSA Autoantibody System — Journal of Immunology Research
  23. Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythematosus — The New England Journal of Medicine
    Posted on June 29, 2023
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    Neil J. Gonter, M.D. is an assistant professor of medicine at Columbia University. Learn more about him here.
    Bora Lee, Ph.D. has more than 10 years of translational research experience in reproductive medicine and women’s health, with a focus on fertility and placental health. Learn more about her here.

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