If your doctor thinks you might have lupus, one of the first tests they’ll likely order is an antinuclear antibody (ANA) test. This blood test looks for autoantibodies — proteins made by the immune system that mistakenly attack healthy cells. Almost everyone who’s eventually diagnosed with lupus has a positive ANA test result.

However, what if you have a negative ANA test but still have symptoms that look like lupus or another autoimmune disease? Although it’s less likely, it’s still possible to be diagnosed with lupus in this case. Some people may also be told they have “borderline lupus” — a term used when symptoms suggest lupus but don’t fully meet the criteria for diagnosis.

Having lupuslike symptoms with a negative ANA test can feel confusing and frustrating. This article explains what the ANA test measures, why it matters for lupus diagnosis, and what your options are if your test is negative but your symptoms continue.

What Is an Antinuclear Antibody Test?

To understand an antinuclear antibody test, it helps to break down the name. An antibody is a molecule made by your immune system to fight off harmful invaders like viruses or bacteria. In autoimmune diseases, the body makes autoantibodies — antibodies that mistakenly attack healthy cells. An “antinuclear” antibody targets a cell’s nucleus. The nucleus is like the cell’s control center — it holds DNA, which contains instructions for how your body grows and functions.

If you have antinuclear antibodies, they may be found in your bloodstream. Your healthcare provider will draw a blood sample and send it to a lab. There are two common ways to run an ANA test — indirect immunofluorescence and solid-phase assay.

Indirect Immunofluorescence

In this type of ANA test, your blood is diluted many times, often starting at a ratio of 1-to-10 and continuing to 1-to-1,280 or more. The diluted blood is placed on a slide that has cells attached. If your blood has autoantibodies, they’ll stick to these cells.

Indirect immunofluorescence tests typically have two parts:

• ANA titer — This number shows how many antibodies were found. The higher the ANA titer, the more antinuclear antibodies you have.
• Fluorescence pattern — This describes how the antibodies appear under the microscope. The pattern can provide clues about which autoimmune disease may be involved.

Each lab has its own normal range, but 1-to-160 is a common cutoff for a positive result.

Solid-Phase Assay

In this ANA test, pieces of cells are attached to a solid surface. Your blood is tested to see if it reacts to any of these cell parts. For each target, the results are reported as positive, negative, or indeterminate (unclear).

Solid-phase assays are faster than indirect immunofluorescence and can identify specific autoantibodies linked to certain autoimmune diseases. However, the assays may not detect all patterns.

Why Is the ANA Test Important for Lupus Diagnosis?

The ANA test is usually one of the first tests your healthcare provider orders if they think you might have lupus. About 98 percent of people with systemic lupus erythematosus (SLE), the most common type of lupus, test positive for antinuclear antibodies. The ANA test is a screening tool that can lead to more testing and evaluation.

However, a positive ANA test by itself doesn’t mean you have lupus. Many people without autoimmune conditions can still have antinuclear antibodies. Around 15 percent of healthy people may have a positive ANA test.

Also, ANA test results can change over time. This is why the ANA test should be interpreted by your healthcare provider, who is familiar with your medical history and symptoms.

How Is Lupus Diagnosed?

Lupus is diagnosed based on your test results and your symptoms. A positive ANA test is one of the requirements for diagnosis, according to guidelines from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

After an ANA test, your healthcare provider may order more blood tests and urine tests to help confirm a diagnosis or rule out other conditions.

Additional Blood Testing

Your rheumatologist (a specialist in autoimmune diseases) may order these follow-up tests:

• Additional autoantibody testing — Looks for specific antibodies linked to lupus, such as anti-dsDNA, anti-Ro/SSA, and anti-La/SSB
• Complete blood count (CBC) — Evaluates your red blood cells, white blood cells, and platelets, which can be affected by lupus
• Complete metabolic panel (CMP) — Assesses how well your kidneys, liver, and other organ systems are working
• Complement levels (C3 and C4) — Checks levels of complement proteins, with low levels suggesting active disease or a flare
• Erythrocyte sedimentation rate (ESR) — Detects general inflammation in your body
• C-reactive protein (CRP) — Indicates inflammation and may reflect more acute or recent changes than ESR
• Urinalysis — Screens for protein or blood in the urine, which may signal kidney involvement, a common complication of lupus

If your ANA test is negative but other results suggest lupus, your diagnosis may be more complex.

Can You Still Have Lupus With a Negative ANA Test?

According to lupus diagnostic criteria from the EULAR and ACR, a lupus diagnosis requires a positive ANA test result. However, in real-world practice, some rheumatologists (specialists in autoimmune and inflammatory diseases) might describe your condition as lupus even with a negative ANA result. Others might use broader terms such as:

• Borderline lupus
• Mixed connective tissue disease
• Forme fruste lupus (a milder or incomplete version of the disease)

No matter the label, your healthcare team will focus on treating your symptoms and supporting your health.

When a Negative ANA Test Doesn’t Rule Out Lupus

In certain cases, people with a negative ANA test can still be diagnosed with lupus. For example, it’s possible to test negative but still have positive results for other lupus-specific autoantibodies, such as anti-Sm antibodies. Doctors may still diagnose lupus based on the full picture of lab results and symptoms.

Also, labs don’t all run and interpret ANA tests the same way. That means your result might be reported as negative even when low levels of antinuclear antibodies are present — but not clearly detected. In addition, some people are diagnosed with ANA-negative lupus if they have lupus nephritis confirmed by kidney biopsy.

What Are the Next Steps?

If you’ve had an ANA test with a negative result, your rheumatologist will likely order additional tests to better understand what’s causing your symptoms. Reaching a clear diagnosis can take a while, especially when symptoms overlap with those of other autoimmune diseases.

Even if you don’t meet the full criteria for a lupus diagnosis, your treatment may still involve similar approaches, especially if your symptoms are consistent with lupus. Throughout this process, it’s important to stay in open communication with your healthcare team about your test results, symptoms, and treatment plan.

Talk With Others Who Understand

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

Are you experiencing symptoms of lupus? Have you had a negative ANA test, and aren’t sure what happens next? Share your experience in the comments below, or start a conversation by posting on your Activities page.