When blood tests are negative

Many people with Sjögren’s disease test negative for anti-SSA (Ro) and anti-SSB (La) antibodies. This article explains what seronegative Sjögren’s means, how diagnosis works when blood tests are negative, and what current research says about these cases.
 

What does “seronegative” mean?

Most people associate Sjögren’s disease with the blood tests for anti-SSA (Ro) and anti-SSB (La) antibodies. But not everyone with Sjögren’s has these antibodies. If your tests are negative, doctors call this seronegative Sjögren’s.

Research shows this is not rare. In fact, about 15 to 30 percent of people diagnosed with Sjögren’s are seronegative.

This means up to one in three people could be missed if diagnosis relied on blood tests alone.

Diagnosis is more than a blood test

Sjögren’s is a complex autoimmune condition that affects moisture-producing glands, but diagnosis is never based on one test.

The 2016 ACR-EULAR Classification Criteria for Sjögren’s disease include several types of testing. Doctors look for a combination of results, such as:

• Lip (minor salivary gland) biopsy to check for inflammation
• Eye tests like the Schirmer’s test or ocular surface staining
• Saliva flow measurements to see how well glands are working
• Salivary gland ultrasound to look for changes inside the glands

You can still meet the definition of Sjögren’s without positive antibodies if these other tests show clear signs of gland involvement.

Lip biopsy: a key tool for diagnosis

When blood tests are negative, a lip biopsy can help confirm Sjögren’s disease. During this test, a small piece of tissue from inside your lower lip is examined for clusters of immune cells (called focal lymphocytic sialadenitis).

A large review found lip biopsy correctly identifies most people with Sjögren’s, even if they’re seronegative (Guellec et al., 2013). More recent studies also show that biopsy results are particularly valuable when antibody tests are unclear.

Ultrasound: a non-invasive alternative

For people who prefer to avoid a biopsy, salivary gland ultrasound (SGUS) is a useful alternative. It can show changes in the size and structure of the glands that suggest inflammation.

Recent studies show SGUS has good accuracy and may be especially helpful for identifying seronegative patients. It is also quick, painless, and widely available in many clinics.

Are seronegative patients different?

Research comparing people with and without antibodies has found some differences. Seronegative patients may be diagnosed slightly later and have fewer immune markers in their blood. However, they experience the same core symptoms of dryness, fatigue, and pain.

In other words, their disease is just as real, and deserves the same level of care and understanding.

Emerging research and new hope

Scientists are continuing to study new biomarkers and antibodies that could make diagnosing Sjögren’s easier in the future.

Early studies have identified promising new antibodies that may help doctors recognize the disease in people who are currently seronegative. While these tests are not yet standard, they point to a more accurate and inclusive future for diagnosis.

What you can do if your tests are negative

If your blood tests are negative but your symptoms match Sjögren’s, you can ask your doctor about:

- A lip (minor salivary gland) biopsy
- Salivary gland ultrasound
- Eye and saliva flow tests

These objective tests can help confirm the diagnosis and ensure you get the right support and care.