Major Laboratory Tests for Systemic Lupus Erythematosus
Begin with antinuclear antibody (ANA) testing using indirect immunofluorescence assay on HEp-2 cells, and if positive, immediately proceed with a comprehensive autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, antiphospholipid antibodies, complement levels (C3, C4), complete blood count, serum creatinine, urinalysis, and urine protein/creatinine ratio. 1, 2
Initial Diagnostic Laboratory Panel
Immunological Tests (Core Autoantibodies)
ANA (Antinuclear Antibody): Perform first as the initial screening test using indirect immunofluorescence assay on HEp-2 cells as the gold standard method 1, 2
Anti-dsDNA antibodies: Use a double-screening strategy with solid-phase assay followed by confirmation with Crithidia luciliae immunofluorescence test for higher specificity; highly specific for SLE and present in 40-80% of patients 1, 2
Anti-Sm antibodies: Highly specific for SLE and must be included in the baseline panel 3, 1, 2
Anti-Ro/SSA and anti-La/SSB antibodies: Essential in the initial panel, particularly critical before pregnancy due to risk of congenital heart block and neonatal lupus 3, 1, 2
Anti-RNP antibodies: Should be part of the comprehensive autoantibody panel 3, 1, 2
Antiphospholipid antibodies: Test for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I to identify patients at risk for antiphospholipid syndrome 3, 1, 2
Complement levels (C3 and C4): Required at baseline and correlate with disease activity, particularly in lupus nephritis; C3 hypocomplementemia rates reach 86% and C4 reaches 64% in active disease 3, 2, 4
Routine Laboratory Tests
Complete blood count (CBC): Mandatory to detect cytopenias including anemia (present in 52-71% of patients), leukopenia (present in 30-57%), lymphopenia (82%), and thrombocytopenia (26-40% with platelets <100 × 10⁹/L) 3, 2, 4, 5
Serum creatinine or estimated glomerular filtration rate: Must be checked at baseline to assess renal function 3, 2
Urinalysis: Essential to detect hematuria, pyuria, or cellular casts 3, 2
Urine protein/creatinine ratio: Should be obtained at baseline to assess for proteinuria, as approximately 40% of SLE patients develop lupus nephritis 1, 2
Erythrocyte sedimentation rate (ESR): Helps distinguish inactive from active disease 2
C-reactive protein (CRP): Should be measured as part of inflammatory marker assessment 2
Serum albumin: Required as part of baseline laboratory tests 2
Critical Pitfalls to Avoid
Do not skip the comprehensive autoantibody panel: Anti-dsDNA and anti-Sm positivity are highly specific for SLE, and missing these can delay diagnosis 1
Do not use solid-phase assays alone for anti-dsDNA: Always confirm positive results with Crithidia luciliae immunofluorescence test for higher specificity 1, 2
Do not forget to check anti-Ro/SSA and anti-La/SSB before pregnancy: These antibodies carry significant risk for congenital heart block and neonatal lupus 1, 2
Do not overlook urine microscopy when urinalysis is abnormal: Cellular casts are critical for diagnosing active lupus nephritis 3, 1
Recognize that thrombocytopenia indicates higher disease activity: Patients with thrombocytopenia have higher mortality rates, more end-organ damage, and increased disease activity 6
Understand that anemia in SLE has multiple etiologies: While anemia of chronic disease is most common (46-66%), autoimmune hemolytic anemia occurs in 14-28% of cases and requires different management 4, 5