What labs are used to screen for rheumatoid arthritis (RA) and lupus?

Laboratory Screening for Rheumatoid Arthritis and Lupus

For rheumatoid arthritis screening, order anti-CCP antibodies and rheumatoid factor; for lupus screening, order ANA by IIFA on HEp-2 cells at 1:160 dilution, followed by anti-dsDNA and complement levels (C3, C4) if ANA is positive. 1

Rheumatoid Arthritis Screening

Primary Tests

• Anti-CCP (anti-cyclic citrullinated peptide) antibodies are the most specific marker for RA, with 95% specificity compared to RF's <90% specificity, while maintaining comparable sensitivity of >70% 2
• Rheumatoid factor (IgM-RF) should be measured quantitatively by nephelometry, as it remains positive in 68-80% of RA patients 3, 4
• Both tests should be ordered together, as anti-CCP and RF used concomitantly improve diagnostic accuracy—among RF-positive patients, approximately 50-60% are also anti-CCP positive 3, 4

Supporting Laboratory Tests

• ESR and CRP to assess inflammatory activity, with CRP correlating more closely with clinical and radiographic parameters of RA inflammation than ESR 5, 1
• Complete blood count with differential to detect cytopenias or anemia that may indicate disease activity 1
• Comprehensive metabolic panel including creatinine/eGFR and albumin to assess baseline organ function 1

Critical Interpretation Points

• Anti-CCP antibodies are detectable very early in disease and predict erosive RA development 2
• High RF titers are associated with progressive joint inflammation, erosions, and disability 5
• Seronegative RA exists—negative RF does not exclude RA, making anti-CCP particularly valuable in these cases 3, 5

Systemic Lupus Erythematosus Screening

First-Line Test

• ANA by indirect immunofluorescence (IIFA) on HEp-2 cells is the reference method for screening systemic autoimmune rheumatic diseases 6, 1
• Screening dilution must be 1:160 on conventional HEp-2 substrates for adults, representing the 95th percentile of healthy controls 6, 1
• Both titer AND pattern (nuclear, cytoplasmic, or mitotic) must be reported, as patterns provide critical diagnostic information 6, 1

Reflex Testing When ANA is Positive

• Anti-dsDNA antibodies should be ordered when SLE is clinically suspected—levels >300 IU/mL indicate high disease activity requiring aggressive immunosuppression 7, 1
• Complement levels (C3, C4) are essential for SLE evaluation and monitoring, as low complements with high anti-dsDNA indicate active disease 7, 1
• Specific antibody panel including anti-Ro (SSA), anti-La (SSB), anti-RNP, and anti-Sm based on clinical presentation and ANA pattern 6, 1
• Anti-phospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) if thrombosis, recurrent pregnancy loss, or thrombocytopenia is present 1

Additional Baseline Testing for Lupus

• Urinalysis with urine protein/creatinine ratio to detect renal involvement 1
• Complete blood count to detect cytopenias (leukopenia, lymphopenia, thrombocytopenia, anemia) 1
• Comprehensive metabolic panel for renal and hepatic function assessment 1
• Quantitative immunoglobulin levels (IgG, IgA, IgM) to identify immunodeficiency states 1

Critical Pitfalls to Avoid

For ANA Testing

• Never use limited antigen ELISA panels as initial ANA screening—they miss important patterns and have lower sensitivity than IIFA 1
• If automated methods (ELISA, multiplex) are negative but clinical suspicion remains high, IIFA must be performed due to superior sensitivity for SLE 6, 1
• ANA positivity occurs in up to 5% of healthy individuals at 1:160 dilution, so clinical context is essential 1
• A negative ANA does not exclude autoimmune disease—sensitivity is not 100% even at 1:160 dilution 1
• In cases of high clinical suspicion, specific antibody testing should proceed regardless of ANA result (e.g., anti-Ro for neonatal lupus/congenital heart block, anti-ribosomal P for SLE) 6

For Lupus Anticoagulant Testing

• Generalized screening in asymptomatic individuals is highly discouraged due to poor specificity and high false-positive rates 6
• Blood collection should occur before anticoagulant therapy or after sufficient discontinuation period 6
• If lupus anticoagulant is positive, testing must be repeated >12 weeks after initial testing for confirmation 6

For RA Testing

• Anti-CCP is more specific than RF (95% vs <90%), making it particularly valuable when RF is negative or equivocal 2
• RF is nonspecific and can be positive in up to 15% of healthy individuals and other disorders 3, 5

Special Populations

• Before pregnancy: Check anti-Ro and anti-La antibodies due to risk of congenital heart block, and anti-phospholipid antibodies 1
• Children under 16 years: No consensus exists for ANA screening dilution—some laboratories use 1:40 instead of 1:160 1
• Before immunosuppressive therapy: Screen for infectious diseases (HIV, hepatitis B/C) based on risk factors, and tuberculosis per local guidelines 1