What to Know About ANA-Negative Lupus

Debating whether it is lupus or other overlapping medical conditions

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ANA-negative lupus is a rare situation in which a person is said to have lupus—otherwise known as systemic lupus erythematosus (SLE)—but a blood test used to confirm lupus comes back negative. The test, known as an antinuclear antibody (ANA) test, detects a protein called antinuclear antibody (ANA) typically found in people with lupus and other autoimmune diseases.

Although almost everyone with lupus has the antibody, a positive ANA result doesn't necessarily mean that you have lupus. On the flip side, a negative result doesn't necessarily mean that you don't have lupus.

This article explains what ANA-negative lupus means, how common it is, and the possible reasons for a negative ANA result.

An illustration with information about "Does ANA-Negative Lupus Exist?"

What Is Lupus?

Systemic lupus erythematosus (lupus) is a chronic (long-lasting) autoimmune disease that can affect many parts of the body.

As with other autoimmune diseases, lupus is caused by an immune system that has gone awry. Rather than protecting the body from disease and infection, the immune system "turns on itself" and attacks its own cells and tissue, causing inflammation and tissue damage.

Lupus is called systemic because it attacks the body as a whole. Many organs can be affected by lupus, including the skin, joints, heart, lungs, kidneys, circulating blood cells, and brain.

Lupus can directly cause, among other things:

How Lupus Is Diagnosed

No single test can diagnose lupus, and it often takes time to reach a definitive diagnosis. The diagnosis starts with a review of your medical history and family history, a physical exam, and the antinuclear antibody (ANA) test.

A positive result from an ANA test (meaning that the antibody was detected in your blood) is strongly suggestive of lupus. But since ANA is also found in autoimmune diseases like rheumatoid arthritis and scleroderma, it doesn't necessarily mean that you have lupus.

To confirm the diagnosis, another test—called a multianalyte panel (MAP) of autoantibodies—would be performed to help distinguish it from other autoimmune diseases. On its own, a MAP test (known commercially as AVISE Lupus) is 80% accurate in correctly diagnosing lupus.

Other blood and urine tests would be performed to diagnose conditions associated with lupus (like low blood counts and kidney dysfunction). In their entirety, these findings can help support the diagnosis.

On the flip side, a negative result from an ANA (meaning that the antibody was not detected in your blood) usually rules out lupus as a cause. But not always, according to some experts.

What Is ANA-Negative Lupus? 

The ANA test is interpreted based on the antibody titers (or the concentration of the antibodies in a sample of blood). The titer is reported in the ratios like 1:40, 1:60, 1:80, 1:160, 1:320, and 1:640.

Most labs report that an ANA test is positive when it is 1:160 or above. According to the American College of Rheumatology (ACR), the test may be considered positive at 1:80 or above when accompanied by at least one other characteristic of lupus, like nephritis or myocarditis.

Generally, anything under 1:80 is considered negative.

With that said, it is possible for a person to have a low-titer ANA result and still have symptoms consistent with lupus. This is referred to as ANA-negative lupus.

Debating ANA-Negative Lupus

ANA-negative lupus is rare. Studies suggest that up to 2% of people with lupus fall within the broad definition of a condition still under debate by health experts.

While some people regard ANA-negative lupus as a category of SLE, others (including the ACR) have resisted classifying it as such. In such instances, the spectrum of symptoms may be referred to as:

On one side of the fence, the ACR reports that between 99.3% and 99.6% of people with lupus have a positive ANA test. While the organization acknowledges that some people with lupus-like symptoms have negative ANA results, they argue that the phenomenon needs further research to determine if lupus or some other condition (or overlapping conditions) are involved.

On the other side of the fence, many experts argue that there has yet to be any testing method that is 100% accurate for lupus, including the ANA test.

Moreover, they contend that the vast majority of studies have identified people who fall under the umbrella of ANA-negative lupus, the vast majority of whom do not get treatment because the current criteria exclude lupus as a cause.

Takeaway

In short, the medical community cannot agree as to whether ANA-negative lupus truly exists as a medical condition. Most use it as a way to explain an illness that mimics lupus (or may be lupus) but can’t unequivocally be diagnosed as lupus.

Summary

ANA-negative lupus is a rare condition in which a person has lupus-like symptoms but test results are negative for an antibody found in almost all people with lupus (called antinuclear antibody or ANA).

Some studies suggest that up to 2% of lupus cases are ANA-negative. Even so, health authorities have resisted classifying it as a subcategory until further research determines whether lupus is the cause or if is due to unrelated, overlapping disorders.

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7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Jeri Jewett-Tennant, MPH
Jeri Jewett-Tennant, MPH, is a medical writer and program development manager at the Center for Reducing Health Disparities.