What labs are used to diagnose autoimmune etiology?

Laboratory Tests for Diagnosing Autoimmune Etiology

The diagnosis of autoimmune diseases requires specific laboratory tests including antinuclear antibodies (ANA) by indirect immunofluorescence as the gold standard screening test, followed by disease-specific autoantibodies and inflammatory markers. 1, 2

Core Laboratory Tests for Autoimmune Disease Evaluation

First-Line Testing

• Antinuclear Antibodies (ANA)

  • Gold standard method: Indirect immunofluorescence assay (IIFA) on HEp-2 cells 1
  • Screening dilution: 1:160 for adults being evaluated for systemic autoimmune diseases 2
  • Patterns and titers are clinically significant (higher titers ≥1:160 have stronger associations with autoimmune diseases) 2

• Complete Blood Count with Differential

  • Evaluates for cytopenias (common in autoimmune diseases)
  • Assesses for leukocytosis (indicating inflammation)

• Inflammatory Markers

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Complement levels (C3, C4) - low levels seen in active autoimmune disease 2

Disease-Specific Autoantibody Testing

For Systemic Autoimmune Diseases

• Anti-double stranded DNA (anti-dsDNA) - specific for SLE
• Extractable nuclear antigens (ENA) panel:
  • Anti-Ro/SSA and Anti-La/SSB (Sjögren's syndrome)
  • Anti-Smith (SLE)
  • Anti-RNP (Mixed connective tissue disease)
  • Anti-Scl-70 (Systemic sclerosis)
  • Anti-Jo-1 (Polymyositis/dermatomyositis)

For Autoimmune Hepatitis

• Smooth muscle antibodies (SMA)
• Anti-liver kidney microsome type 1 (anti-LKM1)
• Anti-liver cytosol type 1 (anti-LC1)
• Anti-soluble liver antigen (anti-SLA) 1, 2

For Autoimmune Neurological Diseases

• CSF analysis including:
  • Cell count and differential
  • Protein and glucose levels
  • IgG index and oligoclonal bands
  • Neuronal autoantibody panels 1

Testing Methodology Considerations

ANA Testing

• IIFA remains the reference method for ANA detection 1
• ELISA and other solid-phase assays may be used but have limitations:
  • Not recommended as sole primary screening tests 1
  • May miss certain autoantibody patterns visible on IIFA 1

Testing Algorithm

1. Initial screening: ANA by IIFA
2. If positive: Proceed with specific autoantibody testing based on clinical presentation
3. If negative but strong clinical suspicion: Consider disease-specific antibodies that may be negative on ANA screen 2

Important Considerations

• Autoantibody titers may vary during disease course; seronegative individuals at diagnosis may express conventional autoantibodies later 1
• Up to 60% of initially antibody-negative patients may show seroconversion within 5 years 2
• Tissue biopsy (e.g., liver, kidney, affected organ) is often necessary to confirm diagnosis 1, 2
• Test results must be interpreted in clinical context - up to 25% of healthy individuals can be ANA positive 1

Pitfalls to Avoid

• Do not rely solely on solid-phase assays (ELISA) for initial screening as they may miss certain autoantibodies 1
• Do not diagnose based on weakly positive ANA results without clinical correlation 2
• Do not repeat ANA testing routinely for disease monitoring - it's primarily for diagnosis 2
• Do not collect blood samples after immunoglobulin treatment or plasmapheresis to avoid false results 1
• Do not interpret results outside clinical context - laboratory findings must be correlated with symptoms 2

For suspected autoimmune encephalitis, cerebrospinal fluid analysis is the most important test and should be performed regardless of MRI findings unless contraindicated 1.