Laboratory Tests for Diagnosing Sjögren's Syndrome
The diagnosis of Sjögren's syndrome requires serological testing for anti-SSA/Ro and anti-SSB/La antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF), along with objective assessments of ocular and salivary gland function. 1
Core Laboratory Tests
Autoantibody Testing
- Anti-SSA/Ro antibodies - Most sensitive serological marker (present in 60-70% of patients) 2
- Anti-SSB/La antibodies - Often co-occurs with anti-SSA/Ro
- Antinuclear antibodies (ANA) - Often positive in Sjögren's syndrome
- Rheumatoid factor (RF) - Frequently elevated
Inflammatory Markers
- C-reactive protein (CRP)
- Erythrocyte sedimentation rate (ESR)
Additional Laboratory Tests
For Suspected Extraglandular Manifestations
- Complete blood count (CBC) - To evaluate for cytopenias
- Comprehensive metabolic panel - To assess liver and kidney function
- Complement levels (C3, C4) - Decreased C4 levels indicate higher risk of developing lymphoma 1
- Cryoglobulins - For suspected vasculitis
- Urinalysis - For renal involvement
For Differential Diagnosis
- Thyroid function tests - To rule out thyroid disease
- Hepatitis C antibodies - Can cause sicca symptoms mimicking Sjögren's
Emerging Biomarkers
- Novel early biomarkers - Antibodies to salivary gland protein-1 (SP-1), parotid secretory protein (PSP), and carbonic anhydrase VI (CA-6) may appear earlier in disease course and are often positive when traditional markers are negative 3
- Alpha-fodrin autoantibodies - May be useful in patients with negative anti-Ro/SSA and anti-La/SSB 4
Diagnostic Criteria Context
According to the American College of Rheumatology and European League Against Rheumatism criteria, a score of ≥4 is required for diagnosis based on these weighted criteria 1:
| Criterion | Weight |
|---|---|
| Anti-SSA/Ro antibody positivity | 3 |
| Focal lymphocytic sialadenitis on labial salivary gland biopsy | 3 |
| Abnormal ocular staining score | 1 |
| Schirmer test ≤5 mm/5 minutes | 1 |
| Unstimulated salivary flow rate ≤0.1 ml/minute | 1 |
Clinical Pearls
- Autoantibodies may be present up to 18-20 years before clinical diagnosis of Sjögren's syndrome 5
- Anti-Ro/SSA and anti-La/SSB antibodies are associated with earlier disease onset and extraglandular manifestations 2
- Patients may present with neurological manifestations without classic sicca symptoms, requiring high clinical suspicion 6
- Regular monitoring for lymphoproliferative disorders is essential, as patients have a 20-fold increased risk of developing non-Hodgkin lymphoma 1
Common Pitfalls to Avoid
- Relying solely on traditional biomarkers - Up to 40% of patients may be seronegative for traditional markers, especially in early disease
- Missing extraglandular manifestations - Laboratory tests should be guided by symptoms suggesting systemic involvement
- Overlooking pulmonary involvement - Serologic biomarkers should not be used to evaluate for pulmonary involvement; instead, detailed clinical assessment and appropriate imaging are recommended 7
- Failing to exclude other causes of sicca symptoms - Always consider medication side effects, sarcoidosis, IgG4-related disease, and other autoimmune conditions
By following this comprehensive laboratory approach, clinicians can effectively diagnose Sjögren's syndrome and identify patients at risk for complications, allowing for timely intervention and improved outcomes.