How to Diagnose Sjögren’s Syndrome: A Comprehensive Guide

Sjogren's Syndrome


Are you wondering how Sjögren’s syndrome is diagnosed? What tests and antibodies are used? What are the diagnostic criteria? And is it possible to have Sjögren’s disease even if your antibodies are negative? In this comprehensive guide, Dr. Diana Girnita, a board-certified rheumatologist and autoimmune expert, answers these questions in detail to help you better understand the diagnosis of Sjögren’s syndrome.

Antibodies Used to Diagnose Sjögren’s Disease

The most common antibodies seen in patients with Sjögren’s disease include:

  • Positive ANA (antinuclear antibodies)
  • Positive anti-SSA/anti-Ro or SSB/anti-La
  • Positive Rheumatoid factor (RF)
  • More rarely, positive anti-centromere antibodies ( also seen in limited systemic sclerosis or scleroderma)
  • Even more rarely, anti-CCP antibodies (seen in rheumatoid arthritis)
  • In patients with nervous system manifestations like transverse myelitis or neuromyelitis optica, anti-aquaporin 4 antibodies may also be present.

Interpreting Antibody Test Results

A positive ANA (antinuclear antibodies) with a speckled pattern can indicate Sjögren’s disease in patients with suggestive clinical symptoms. According to a recent study published in May 2024, higher titers of ANA, SSA, and SSB antibodies are associated with more inflammation and a higher risk of developing organ damage.

It’s important to note that some patients may be ANA-negative but still test positive for SSA and SSB antibodies. In such cases, if you have dry eyes, dry mouth, or other symptoms, your doctor should order tests for ANA, SSA, and SSB antibodies.

Between 60-80% of patients with Sjögren’s disease have one or both SSA and/or SSB antibodies present, and having both antibodies increases the risk of a more severe disease.

What Other Antibodies can be positive in Sjogren’s Disease?

Anti-centromere antibodies can be present in 5% of Sjögren’s disease patients.

Some patients may test positive for SSB but not SSA antibodies, which, according to a 2015 study, does not necessarily indicate a specific manifestation or worse/better disease course.

A 2017 study showed that some of Sjögren’s patients have aquaporin antibodies (different from aquaporin-4) even without neurological symptoms.

Patients with neurological complaints like neuromyelitis optica may have aquaporin-4 antibodies, which are specific to this condition.

The Early Sjögren Panel, which tests for antibodies to murine parotid tissue proteins, is debated in the rheumatology world due to the lack of validation as markers of early Sjögren’s disease. Further research is needed to determine its utility.

Other Diagnostic Tests

Diagnostic Tests for sjogren's syndromeIn addition to antibody tests, other laboratory tests may be ordered, including:

  • Complete blood count (CBC) to check for anemia, low white blood cells, or low platelets
  • Markers of inflammation like erythrocyte sedimentation rate (ESR)
  • Serum electrophoresis
  • Complement levels (C3, C4)
  • Hepatitis B, C, TB, and HIV tests to rule out other potential causes of Sjögren’s-like symptoms

To assess dry mouth, tests like 

  • salivary gland scintigraphy
  • sialometry, and 
  • salivary gland imaging (ultrasonography or MRI) may be performed.

For dry eyes, tests like

  • Schirmer test (measuring tear production) and 
  • Ocular surface staining (using dyes like Rose Bengal or fluorescein/lissamine green to detect damage) are commonly used.

A labial salivary gland biopsy is an important tool for diagnosing Sjögren’s disease, especially when other signs of autoimmunity are absent. 

A positive biopsy, showing focal lymphocytic sialadenitis with a focus score ≥1, is found in around 66-89% of diagnosed cases.

Diagnostic Criteria for Sjögren’s Disease

In 2016, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) released new criteria for the classification of primary Sjögren’s disease.

Based on a points system for different criteria, a diagnosis can be established. 

  • A positive labial salivary gland biopsy (3 points)
  • A positive SSA antibody (3 points)
  • ocular tests (1 point)
  • salivary tests (1 point)

Individuals are classified as having Sjögren’s disease if they have a score of 4 or higher.

Can You Have Sjögren’s Disease Without Positive Antibodies?

Yes, it is possible to have Sjögren’s disease without positive antibodies, according to the 2016 ACR/EULAR criteria and other studies.

A 2021 study found that about 

  • 8% of Sjögren’s patients had negative SSA, SSB, and RF but positive ANA.
  • Around 4.5% of patients were negative for all antibodies (SSA, SSB, RF, and ANA).

A recent 2023 study involving more than 900 Sjögren’s patients revealed that about 32% were negative for both SSA and SSB antibodies.

Compared to antibody-positive patients, the seronegative patients were:

  • More likely to be male (90% vs. 76% in females)
  • Had a higher proportion of abnormal Schirmer tests (96% vs. 89%, p=0.001)
  • Had more frequent interstitial lung disease (ILD) (59% vs. 28.8%, p=0.001)

This highlights the importance of considering antibody-negative cases, especially in males, as their diagnosis can be more challenging.

If you’re experiencing symptoms suggestive of Sjögren’s disease, such as dry eyes, dry mouth, fatigue, or joint pain, don’t hesitate to seek professional help. Rheumatologist OnCall offers expert consultations and guidance on diagnosing and managing autoimmune diseases like Sjögren’s. Visit our website or call 6505254404 to schedule an appointment with a board-certified rheumatologist today.

Remember, early diagnosis and proper management are crucial for managing the symptoms and complications of Sjögren’s disease. Take the first step towards better health by consulting with a rheumatology specialist.


Q: If I don’t have positive antibodies, can I still be diagnosed with Sjögren’s disease?

A: Yes, the 2016 ACR/EULAR criteria allow for a diagnosis based on a combination of factors, even without positive antibodies.

Q: Are there any differences in symptoms between antibody-positive and antibody-negative Sjögren’s patients?

A: Research suggests that antibody-negative patients may have a higher prevalence of abnormal eye dryness tests and interstitial lung disease.

Q: As a male, should I be more concerned about antibody-negative Sjögren’s disease?

A: Yes, studies have shown that males are more likely to be antibody-negative but can still develop Sjögren’s disease. If you experience symptoms, discuss your concerns with your rheumatologist.

Q: What additional tests might be recommended for antibody-negative Sjögren’s disease?

A: Depending on your symptoms, your rheumatologist may recommend pulmonary function tests or a high-resolution CT scan to evaluate for potential complications like interstitial lung disease.



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