A very small number of people who test negative for antinuclear antibody (ANA) in the blood, which is a sign of the most common type of lupus, still have the condition.

Lupus is an autoimmune disease that can cause problems with many organs, such as your skin, kidneys, and joints.

According to the Centers for Disease Control and Prevention (CDC), it’s estimated that 5.1 people per 100,000 in the United States are diagnosed with lupus each year. Women are diagnosed more frequently than men.

Lupus is difficult to diagnose since no one test can provide a definitive diagnosis and the disease is highly variable. Doctors use a combination of tests and procedures including:

  • examining your personal and family medical history
  • asking you about your symptoms
  • examining you for characteristic signs of lupus
  • excluding other diseases (autoimmune, infectious, cancers) that can cause a lupus-like picture
  • ordering blood and urine tests
  • ordering skin and kidney biopsies

The most common type of lupus is called systemic lupus erythematosus (SLE). One of the characteristic signs of SLE is an antinuclear antibody (ANA) in your blood. ANA is found in the blood of about 96.8–99.8% of people with SLE.

A small percentage of people can test negative for ANA but still have SLE. In some cases, this is due to the type of test used, as some are more effective than others at detecting ANA. When this happens, it’s called seronegative lupus or ANA-negative lupus.

What is an ANA test?

A type of white blood cell called a B cell produces antibodies when it detects harmful cells or microbes. Antibodies neutralize these perceived threats and signal other immune cells to destroy them.

In people with lupus, white blood cells mistake healthy cells as harmful. This autoimmune reaction produces a type of antibody called ANA (anti-nuclear antibody). ANA are also found in the blood of people with some other autoimmune diseases like Sjögren disease and scleroderma.

Doctors measure levels of ANA with an ANA blood test. About 96.8–99.8% of people with SLE have ANA in their blood. However, testing positive for ANA isn’t enough for an SLE diagnosis.

According to the American College of Rheumatology (ACR), up to 15% of people without a definite autoimmune disease also test positive for ANA. ANAs can appear in the blood years before a clinical disease develops.

It’s important to note that COVID-19 infections can also trigger autoantibodies like ANA, and they can persist for prolonged period of time.

The signs and symptoms of SLE for people with ANA-negative SLE are similar to those for people with ANA-positive SLE.

Signs and symptoms of SLE can include:

In a 2022 study, researchers found that a low platelet count was more prevalent among ANA-negative SLE than ANA-positive SLE.

Two ANA-negative SLE case studies

In a 2020 case study, researchers reported on a 28-year-old man with ANA-negative SLE. He presented with:

  • a butterfly-shaped rash on his face
  • severe swelling in his legs
  • abnormal amounts of protein in his urine

In another 2020 case study, researchers reported on a 45-year-old female who presented with:

  • dry cough
  • worsening breathlessness
  • mild paleness
  • swelling in her leg
  • a non-healing ulcer on her ankle

SLE is caused by an autoimmune reaction where your immune system attacks healthy cells in your body. Researchers do not know why this happens, but a combination of genetics and environmental factors are thought to play a role.

Some people with SLE don’t have ANA in their blood, but they may have other types of antibodies that suggest an autoimmune reaction.

Other autoantibodies include:

  • anti-double stranded DNA bodies, specific to lupus
  • anti-Sm antibodies, specific to lupus
  • anti-Ro and anti-La antibodies
  • anti-histone antibodies
  • anti-RNP antibodies
  • anti-ribosomal P antibodies, specific to lupus

In one 2020 study, research suggests that ANA-negative SLE is particularly common with prolonged use of glucocorticoids or immunosuppressants.

If you have recurrent oral ulcers, Raynaud’s, and glomerular nephritis, with low complements, you may be diagnosed with ANA-negative lupus.

There are no diagnostic criteria for SLE, only several Classification Criteria, the most recent being the 2019 criteria from the ACR and European League Against Rheumatism (ELAR), which requires a positive ANA test at least once to classify an autoimmune disease as SLE.

Under this system, ANA-negative lupus would not meet classification criteria to enroll in a clinical trial.

SLE doesn’t have a cure, but medications can help you manage your symptoms. The treatments for seronegative lupus are the same as SLE. Your doctor may recommend treatments like:

It’s important to see a doctor any time you notice potential symptoms of lupus like a butterfly-shaped rash on your face or an unexplained fever. Regular follow-ups are also essential. It’s critical to tell the doctor if:

  • you develop new symptoms
  • your medications lose their effect
  • your symptoms are getting worse
Medical emergency

Lupus can cause many severe complications. Call emergency medical services or go to the nearest emergency room if you notice potentially life threatening complications like:

The outlook for people with SLE varies widely, but it has improved significantly over the last several decades. Recent studies have reported 5-year survival rates over 93% compared to under 50% in the 1950s.

With proper treatment, many people with SLE live a full typical lifespan.

It is important to note that the leading causes of early death are:

  • cardiovascular disease
  • infections
  • kidney disease

Lupus is often referred to as “the great imitator” since it’s mistaken for other diseases in as many as 40% of cases.

Some of the conditions that lupus can mimic include:

Most people with lupus test positive for ANA, but sometimes anti-nuclear antibodies are found in people without autoimmune disease.

A small number of people with lupus do not have ANA circulating through their blood. It’s also possible to have a positive ANA test and then not have detectable levels of ANA on future tests.