What laboratory tests are included in an autoimmune workup?

Laboratory Tests for Autoimmune Workup

Begin with a complete blood count with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel, and antinuclear antibody (ANA) as the essential first-line screening tests for any suspected autoimmune disease. 1, 2, 3

Initial Screening Panel

The foundational autoimmune workup should include:

• Complete blood count (CBC) with differential to detect cytopenias (anemia, thrombocytopenia, leukopenia) that commonly occur in autoimmune conditions 4, 1, 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to quantify inflammatory activity and monitor disease progression 4, 1, 2
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin), kidney function (creatinine, eGFR), and electrolytes to assess organ involvement 1, 2
• Antinuclear antibody (ANA) as the primary screening tool for systemic autoimmune diseases, with a clinically significant cutoff of 1:40 in adults (1:10-1:20 in children under 18 years) 4, 1, 2

Disease-Specific Autoantibody Panel

For Suspected Systemic Lupus Erythematosus or Connective Tissue Disease

Order the following targeted antibodies at baseline 4, 1:

• Anti-double stranded DNA (anti-dsDNA) - specific for SLE and correlates with disease activity 4, 1
• Anti-Smith (anti-Sm) - highly specific for SLE 4, 1
• Anti-RNP - associated with mixed connective tissue disease 4, 1
• Anti-SSA (Ro) and anti-SSB (La) - associated with Sjögren's syndrome and neonatal lupus; recheck before pregnancy if initially negative 4, 1
• Anti-phospholipid antibodies (anticardiolipin, anti-β2 glycoprotein I, lupus anticoagulant) - recheck before pregnancy, surgery, or with new neurological/vascular events 4
• Complement levels (C3, C4, CH50) - low levels indicate active disease and consumption 4, 1

For Suspected Autoimmune Hepatitis

The liver-specific autoantibody panel includes 4, 2:

• Anti-smooth muscle antibody (SMA) - characteristic of AIH type 1, with VGT pattern (vessels, glomeruli, tubules) being most specific 4
• Anti-liver/kidney microsomal antibody type 1 (anti-LKM-1) - diagnostic for AIH type 2 4
• Anti-liver cytosol type 1 (anti-LC1) - associated with AIH type 2 4
• Anti-mitochondrial antibody (AMA) - specific for primary biliary cirrhosis 4
• Serum immunoglobulins - elevated IgG is characteristic of autoimmune hepatitis 2

For Suspected Inflammatory Myositis

Order muscle enzyme markers 1, 2:

• Creatine kinase (CK) - most sensitive marker for muscle inflammation 1, 2
• AST, ALT, LDH, and aldolase - additional markers of muscle damage 1, 2
• Troponin - to evaluate for myocardial involvement 1, 2

Hemolysis-Specific Workup

If autoimmune hemolytic anemia is suspected based on anemia with elevated reticulocyte count, order 4:

• Peripheral blood smear - look for spherocytes, schistocytes, or macrocytosis 4
• LDH, haptoglobin, indirect bilirubin - markers of hemolysis 4
• Direct antiglobulin test (Coombs test) - confirms immune-mediated hemolysis 4
• Reticulocyte count - should be elevated in hemolysis 4
• Autoimmune serology panel - to identify underlying autoimmune disease 4

Additional Considerations

Urinalysis and Renal Assessment

• Urinalysis with microscopy - detect proteinuria, hematuria, or cellular casts indicating renal involvement 4
• Urine protein-to-creatinine ratio - quantify proteinuria 4

Infectious Disease Screening Before Immunosuppression

Screen for the following before initiating corticosteroids or other immunosuppressive therapy 4:

• HIV, hepatitis B and C - based on risk factors 4
• Tuberculosis - according to local guidelines, especially before high-dose corticosteroids 4

Common Pitfalls to Avoid

• Do not rely solely on autoantibody testing without clinical correlation - ANA can be positive in healthy individuals at low titers, and clinical context is essential 2
• Do not delay treatment while awaiting complete diagnostic workup in severe presentations - initiate corticosteroids promptly in life-threatening situations 1, 2
• Do not order every autoantibody indiscriminately - use clinical presentation to guide targeted testing, as this improves specificity and reduces false positives 4
• Do not forget to screen for infections before starting immunosuppression - this prevents life-threatening opportunistic infections 4, 2

Monitoring During Treatment

For patients on immunosuppressive therapy, monitor at 6-12 month intervals 4:

• Complete blood count 4
• ESR and CRP 4
• Serum albumin and creatinine 4
• Urinalysis and urine protein-to-creatinine ratio 4
• Disease-specific markers (anti-dsDNA/complement for SLE, CK for myositis) 4, 1