What tests and treatments are recommended for a suspected autoimmune disorder, specifically for an autoimmune panel?

Recommended Autoimmune Panel Testing for Suspected Autoimmune Disorders

For suspected autoimmune disorders, a comprehensive autoimmune panel should include antinuclear antibody (ANA) testing by indirect immunofluorescence assay (IIFA) as the reference screening method, followed by specific antibody testing based on clinical presentation and initial results.

Initial Screening Tests

• ANA testing by IIFA on HEp-2 cells should be the first-line screening test for suspected systemic autoimmune rheumatic diseases (SARD), with a screening dilution of 1:160 recommended for optimal sensitivity and specificity 1
• Complete blood count (CBC) with differential to assess for cytopenias common in autoimmune conditions 2
• Inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate disease activity 2
• Comprehensive metabolic panel including liver and kidney function tests to assess for organ involvement 2

ANA Pattern Reporting and Interpretation

• Both nuclear and cytoplasmic staining patterns should be reported when performing ANA-IIFA, as they provide valuable diagnostic information 1
• The pattern and highest dilution demonstrating reactivity should be reported with standardized terminology 1
• Common patterns include:
  • Homogeneous/diffuse (associated with SLE, drug-induced lupus)
  • Speckled (associated with various SARD)
  • Nucleolar (associated with systemic sclerosis)
  • Centromere (associated with limited systemic sclerosis/CREST syndrome) 1

Disease-Specific Antibody Testing

For Positive ANA or Strong Clinical Suspicion:

• Systemic Lupus Erythematosus (SLE):

  • Anti-double-stranded DNA (anti-dsDNA) antibodies - high specificity for SLE 1
  • Anti-Smith (anti-Sm) antibodies - highly specific for SLE 2
  • Complement levels (C3, C4) - often decreased in active SLE 2

• Systemic Sclerosis:

  • Anti-Scl-70/topoisomerase-1 (associated with diffuse cutaneous systemic sclerosis)
  • Anti-centromere (associated with limited cutaneous systemic sclerosis/CREST)
  • Anti-RNA polymerase III (associated with systemic sclerosis with renal crisis) 1, 2

• Sjögren's Syndrome:

  • Anti-SSA/Ro and anti-SSB/La antibodies 1, 2

• Inflammatory Myopathies:

  • Myositis-specific antibodies including anti-Jo-1 and other antisynthetase antibodies
  • Creatine kinase (CK), aldolase, and other muscle enzymes 1, 2

• Mixed Connective Tissue Disease:

  • Anti-U1-RNP antibodies 1, 2

For Suspected Autoimmune Hepatitis:

• Anti-smooth muscle antibodies (SMA) and anti-actin antibodies (type 1 AIH)
• Anti-liver kidney microsome type 1 (anti-LKM1) antibodies (type 2 AIH)
• Anti-soluble liver antigen (anti-SLA) antibodies
• Serum IgG levels 1

For Suspected Autoimmune Neurological Disorders:

• CSF analysis including cell count, protein, glucose, IgG index, and oligoclonal bands
• Neural-specific antibodies based on clinical presentation 1, 3

Important Considerations

• ANA testing is primarily intended for diagnostic purposes, not for monitoring disease progression 1
• Tests based on a restricted mixture of defined nuclear antigens should not be referred to as ANA test or ANA screen 1
• Laboratories should specify the methods used for detecting ANA when reporting results 1
• For anti-dsDNA antibody determination, the Farr assay and Crithidia luciliae immunofluorescence test (CLIFT) offer high clinical specificity 1
• Autoantibody testing should be performed before initiating immunosuppressive therapy when possible, as treatment may affect results 2
• ANA-specific antibodies can sometimes be detected in ANA-negative patients with clinical suspicion of autoimmune disease, so specific antibody testing may still be warranted in these cases 4

Treatment Approach

• Treatment should be tailored to the specific autoimmune condition diagnosed through the testing panel
• Before initiating immunosuppressive therapy, testing for latent tuberculosis and viral hepatitis should be considered 2
• Serial measurements of inflammatory markers and disease-specific antibodies may be useful for monitoring treatment response in some conditions 2

Common Pitfalls to Avoid

• Relying solely on ANA titer without considering pattern or specific antibodies 1, 4
• Using ANA testing for disease monitoring rather than diagnosis 1
• Failing to test for specific antibodies in ANA-negative patients with strong clinical suspicion of autoimmune disease 4
• Not providing sufficient clinical information to the laboratory, which can help guide appropriate test selection 1
• Interpreting positive results without clinical context, as low-titer ANAs can occur in healthy individuals 1