Laboratory Tests for Diagnosing Autoimmune Diseases
The initial laboratory evaluation for suspected autoimmune disease should include inflammatory markers, complete blood count with differential, comprehensive metabolic panel, and autoantibody panels tailored to the clinical presentation. 1
First-Line Laboratory Tests
- Inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be tested to assess disease activity and inflammation 1, 2
- Complete blood count (CBC) with differential to evaluate for cytopenias, which are common in many autoimmune conditions 1, 2
- Comprehensive metabolic panel including liver and kidney function tests to assess for organ involvement 1, 2
- Antinuclear antibody (ANA) testing by indirect immunofluorescence assay (IIFA) as the gold standard screening test for many systemic autoimmune diseases 3
- Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for suspected inflammatory arthritis 1, 2
Disease-Specific Autoantibody Testing
- For suspected systemic lupus erythematosus (SLE): anti-dsDNA, anti-Smith, anti-RNP, anti-SSA, anti-SSB antibodies 1
- For suspected systemic sclerosis: anti-centromere, anti-Scl-70, anti-RNA polymerase III antibodies 1
- For suspected autoimmune hepatitis: anti-smooth muscle antibodies, anti-liver kidney microsomal antibodies, and serum immunoglobulins 1, 2
- For suspected myositis: anti-Jo-1 and other myositis-specific antibodies 1
- For suspected autoimmune encephalitis: neural-specific antibodies and cerebrospinal fluid analysis 3, 1
Organ-Specific Laboratory Tests
- For suspected inflammatory myopathies: creatine kinase (CK), transaminases (AST, ALT), lactate dehydrogenase (LDH), and aldolase 1, 2
- For suspected cardiac involvement: troponin levels 1, 2
- For suspected autoimmune thyroid disease: thyroid function tests (TSH, free T4) and thyroid antibodies (anti-TPO, anti-thyroglobulin) 1
- For suspected celiac disease: tissue transglutaminase and endomysial antibodies 1
Additional Testing Considerations
- Complement levels (C3, C4, CH50) for suspected lupus or complement deficiencies 1
- HLA typing (particularly HLA-B27) for suspected spondyloarthropathies 1
- Cryoglobulins and serum protein electrophoresis for suspected cryoglobulinemic vasculitis 1
- For suspected autoinflammatory syndromes: genetic testing for specific mutations 3, 1
Important Considerations for Testing
- ANA testing should be performed by IIFA on HEp-2 cells as the initial screening method, with a titer of 1:80 or higher considered positive 3
- A positive ANA test alone is not diagnostic as up to 25% of healthy individuals can be ANA positive 3
- Autoantibody testing should be performed before initiating immunosuppressive therapy when possible, as treatment may affect results 1
- Testing for latent tuberculosis and viral hepatitis should be considered before starting immunosuppressive therapy 2
Common Pitfalls to Avoid
- Relying solely on autoantibody testing without clinical correlation can lead to misdiagnosis 2, 4
- False positive test results may lead to inappropriate treatment and unnecessary patient anxiety 4
- Different laboratory techniques for the same antibody test may yield different results (e.g., IIFA vs. multiplex bead assay for ANA) 5
- Autoantibody testing should only be performed in patients with a reasonable clinical suspicion of autoimmune disease, otherwise the predictive value of a positive test is too low 5
Monitoring Disease Activity
- Serial measurements of inflammatory markers (ESR, CRP) should be performed to assess treatment response 1, 6
- Repeat testing of specific autoantibodies may be useful for monitoring disease activity in certain conditions 1, 7
By following this comprehensive laboratory approach, clinicians can effectively diagnose and monitor autoimmune diseases while avoiding common pitfalls in test interpretation.