ANA-Negative Lupus Symptoms and Tests

In simplest terms, ANA-negative lupus is a condition in which a person’s ANA (antinuclear antibody) immunofluorescence (IF) test comes back negative, but the person exhibits traits consistent with someone diagnosed with systemic lupus erythematosus (SLE; also called lupus). The ANA IF test is an important tool in diagnosing lupus.

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Typically, if a person tests positive for the antinuclear antibody, it means only that the person could have lupus. Further tests are needed to determine if a person actually has lupus. Those include tests for double-stranded DNA (dsDNA), Sm (Smith), Ro/SSA (Sjogren's syndrome A), La/SSB (Sjogren's syndrome B), and RNP (ribonucleoprotein) antibodies.

Up to 15% of otherwise healthy people can have a low titer positive ANA. Other tests for inflammation markers (ESR, CRP) and complement levels (C3, C4), may also be obtained.

If the ANA test comes back negative, then it's highly unlikely that the person has lupus.

However, in rare instances, a person will have a negative ANF IF test result but exhibit other traits consistent with lupus.

Antibody tests and symptoms go hand in hand. Antibodies alone do not diagnose the disease.

Does ANA-Negative Lupus Exist?

The general consensus is that ANA-negative lupus is very rare—and is more a term given to patients with “lupus-like” disease. Some physicians might call it “mixed connective tissue disease,” “undifferentiated connective tissue disease,” or “forme fruste lupus”—or “hidden lupus.” Each has specific and separate meaning and describes different forms of illness.

The most current diagnostic criteria for SLE (2019 ACR/EULAR criteria) state that a patient has to have a ANA at a titer of ≥1:80 at least once to be characterized as lupus, otherwise the disease cannot be classified as lupus.

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 be unequivocally diagnosed as lupus.

Put another way, physician Michael D. Lockshin, MD, writes: "The answer to the question, ‘Does ANA-negative lupus exist?’ is technically ‘yes,’ with a large number of buts, and ifs, and whens. Another answer is that the question is not very important. It is never critical to say definitively that a given patient does or does not have lupus. What is important is to evaluate the current symptoms, to put the symptoms into an overall context that includes blood tests, duration of symptoms, other illnesses, and medications, and to develop a treatment plan based on the total information rather than on a blood test alone."

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  1. Grygiel-górniak B, Rogacka N, Puszczewicz M. Antinuclear antibodies in healthy people and non-rheumatic diseases - diagnostic and clinical implications. Reumatologia. 2018;56(4):243-248. doi:10.5114/reum.2018.77976

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.