The ANA Test: Medicine’s Most Misinterpreted Marker

The positive ANA is one of the most common reasons why patients get referred to see a rheumatologist. Unfortunately, the test is also one of the most misunderstood.

Many patients and physicians have the mistaken impression that ANAs always signify rheumatic disease; conversely, if the ANA is negative, they think a rheumatic disease is unlikely. However, many rheumatic diseases do not have a positive ANA, and many diseases that are not rheumatic do.

Here’s a primer to unpack the mysteries of the ANA and learn when to pay attention to it and when to ignore it.

What is an ANA?

Antibodies are sticky proteins that your body makes against foreign microbes to tag them for destruction. Occasionally, however, these antibodies are mistakenly produced against self-proteins, including against the nucleus of your own cells, thus targeting parts of your own cells for destruction. Antibodies that do this are called antinuclear antibodies.

That’s the science. Now the nuance: positive results are surprisingly common. Studies show that up to 15 % of completely healthy adults can have a low‑level ANA. Children often have positive ANAs in the setting of infection—one study showed that more than 50% of children have positive ANAs, and only 8% of them actually had an autoimmune disease. In addition, ANA positivity increases with age, so your grandmother’s positive test doesn’t necessarily mean she has lupus. A positive ANA is a clue, not a diagnosis.

When Does a Positive ANA Matter?

ANAs are most useful in identifying a subset of rheumatic diseases called the connective tissue diseases (CTDs). In these conditions, a negative ANA often rules out the diagnosis, and a high‑titer positive result supports it. Here’s where ANAs really shine:

Connective Tissue Diseases Where ANA Is Often Positive

•Systemic lupus erythematosus (SLE) – Over 95 % of people with lupus have a positive ANA, making it an essential entry criterion.
•Sjögren’s disease – Often linked with ANA positivity; specific antibodies (SSA/Ro and SSB/La) are more diagnostic, but ANA is frequently positive.
•Systemic sclerosis (scleroderma) – Roughly 60–90 % of patients show ANA positivity, sometimes with a centromere pattern that points toward limited cutaneous disease.
•Mixed connective tissue disease (MCTD) – ANA positivity is essentially universal, usually with a speckled pattern and associated anti‑RNP antibodies.
•Dermatomyositis and polymyositis – About half of patients are ANA‑positive . Specific myositis antibodies (e.g., anti‑Jo‑1) may also be present.
•Juvenile idiopathic arthritis (JIA) – ANA‑positive children have a higher risk of eye inflammation and need regular ophthalmology follow‑up.

In these disorders, the absence of ANA makes the diagnosis unlikely, and a higher titer raises suspicion for autoimmune disease.

The ANA Is Not the Only Antibody in the Sea

The ANA test looks for antibodies that target the nucleus of the cell. However, many rheumatic diseases have antibodies against other aspects of the cell, and the ANA test may be negative even when these antibodies are present.

For example, in rheumatoid arthritis, doctors often check for antibodies like anti-CCP or rheumatoid factor, which attack proteins outside the nucleus. In certain types of vasculitis, such as granulomatosis with polyangiitis, the immune system makes antibodies called ANCA that target the cytoplasm of white blood cells. Some muscle diseases, like antisynthetase syndrome, involve antibodies that attack pieces of the machinery inside our cells that help build proteins, which are not located in the nucleus.. And in antiphospholipid syndrome, the body makes antibodies that target blood proteins, which can increase the risk of blood clots.

Rheumatic Diseases That Lack Autoantibodies

Many rheumatic diseases do not have any autoantibodies. The seronegative spondyloarthropathies, for instance, which include psoriatic arthritis, ankylosing spondyloarthritis, among others, are called “seronegative” because no antibodies are found int the serum. Conditions like gout, pseudogout, osteoarthritis, many types of vasculitis, and my favorite—autoinflammatory diseases—do not have autoantibodies, so ANA testing is not useful to diagnose these conditions.

Non‑Rheumatic Causes of ANA Positivity

Finally, a long list of non‑rheumatic conditions can nudge the ANA into the positive range. Low‑titer ANAs may appear in:

•Autoimmune thyroid disease (Hashimoto’s or Graves’ disease) – up to 50 % of patients have ANA positivity.
•Autoimmune liver disease – autoimmune hepatitis and primary biliary cholangitis are often ANA‑positive.
•Chronic infections – tuberculosis, hepatitis C virus, HIV, Epstein–Barr virus, and others can cause transient ANA positivity.
•Medications – certain drugs (hydralazine, procainamide, minocycline, anti‑TNF agents) can induce ANA positivity or even drug‑induced lupus.
•Cancer or blood disorders – some malignancies are associated with autoantibodies.
•Perfectly healthy people – yes, up to 15 %.

A positive ANA in someone who feels well can be the biological equivalent of a smoke alarm chirping without a trace of smoke—more noise than signal. In patients who are on certain medications or living with chronic infections, an experienced rheumatologist understands that such results are often reflections of a broader context, not cause for immediate alarm.

Titer and Pattern: Why the Numbers and Shapes Matter

When the lab reports a positive ANA, it typically lists a titer – something like 1:40, 1:160, or 1:1280. The titer reflects how much antibody exists in the blood Higher titers (≥1:640) are more suggestive of an autoimmune disease, whereas low titers (1:40 or 1:80) are common in healthy individuals.

Labs may also report an ANA pattern, such as homogeneous, speckled, nucleolar, or centromere. These patterns correspond to the staining appearance on the test slide and can hint at certain diseases (e.g., centromere pattern suggests limited scleroderma). Some patterns, such as dense fine speckled, are actually seen in healthy individuals and are not found in people with rheumatic disease. Pattern interpretation is more of an art than a science, and patterns alone cannot diagnose a condition. Your rheumatologist will look for specific autoantibodies (anti‑dsDNA, anti‑Smith, anti‑SSA, etc.) and your symptoms to figure out the next steps.

Common Misconceptions About ANA

Many myths surround ANA testing. Let’s bust a few:

Myth: A positive ANA means I have lupus or another serious disease.
Reality: Most people with a positive ANA do not have lupus. Only about 11–13 % of ANA‑positive individuals develop a connective tissue disease.

Myth: The higher the titer, the sicker I am.
Reality: Higher titers make an autoimmune diagnosis more likely, but they don’t correlate perfectly with disease activity . Some people with stable disease remain highly positive for years, while others with active disease may have moderate titers. Your doctor will monitor specific antibodies and clinical signs to track activity.

Myth: If my ANA is negative, I don’t have an autoimmune disease.
Reality: A negative ANA rules out lupus, scleroderma, MCTD and related CTDs in most cases . But rheumatoid arthritis, psoriatic arthritis and other autoimmune diseases can occur with negative ANA, so your clinician will consider other tests.

Myth: I should repeat my ANA regularly to see if it’s going up or down.
Reality: Once positive, ANA often stays positive, and re‑testing rarely changes management . Doctors focus on your symptoms and specific autoantibodies, not the ANA titer itself.

Myth: Ordering an ANA is a good way to check for general “inflammation” or to see why I’m tired.
Reality: ANA is not a screening test for vague symptoms. It should be ordered only when there are specific signs of a connective tissue disease. Ordering the test indiscriminately can lead to false positives, anxiety, unnecessary referrals and procedures.

When Should I Have an ANA Test?

Doctors order tests based on the story your body tells. An ANA test is appropriate if you have symptoms consistent with CTDs, such as:

•Persistent joint swelling
•Skin rashes (especially those that worsen with sunlight or appear on the cheeks)
•Lymph node enlargement
•Unexplained fevers, fatigue or weight loss
•Difficulty swallowing, tight skin or Raynaud’s phenomenon (fingers turning white/blue in the cold)
•Muscle weakness accompanied by a rash

Conversely, if you have general aches, fleeting fatigue, or “just want to check,” an ANA is rarely helpful.

Pulling It All Together

Imagine the ANA test as a clue in a detective story: it points your physician toward or away from certain possibilities but doesn't solve the case on its own. Many people with a positive ANA will never develop a rheumatic disease, and many rheumatic diseases don't involve ANAs at all. Context – your symptoms, exam findings, and other lab results – is everything. Don't let a lab report falsely alarm you.

Call to Action

If you’ve received a positive ANA or have autoimmune disease symptoms like joint pain, fatigue, rash, or other concerns, the next step isn’t to worry – it’s to consult with a specialist. At Haus Health Rheumatology, we specialize in putting the puzzle pieces together. Our patient‑centered approach focuses on listening to your story, ordering the right tests, and providing evidence‑based guidance. Schedule a consultation to discuss your results and get the clear answers you deserve.