Laboratory Diagnosis of Systemic Lupus Erythematosus

Initial Screening Test

• The American College of Rheumatology recommends that Antinuclear Antibody (ANA) testing should only be performed when clinical suspicion exists, such as unexplained rashes, arthritis, serositis, neurological manifestations, or cytopenias, to avoid false positives in low-prevalence populations 3
• When ANA is negative but clinical suspicion remains high, anti-dsDNA testing may still be pursued, as recommended by the European League Against Rheumatism 1

Confirmatory Immunological Tests

• A double-screening strategy is recommended for anti-dsDNA antibody testing, using a solid-phase assay (SPA) such as FEIA, CLIA, or ELISA, followed by Crithidia luciliae immunofluorescence test (CLIFT) for confirmation, according to the Autoimmunity Reviews guidelines 1, 4
• The American College of Rheumatology suggests that anti-Sm antibodies should be tested as part of an anti-ENA panel when ANA is positive, as they provide strong confirmatory evidence for SLE 1, 5
• The European League Against Rheumatism recommends that anti-ENA panel testing, including anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-RNP, should be performed when ANA is positive, to provide prognostic information for major organ involvement 1, 7

Routine Laboratory Tests

• The Annals of the Rheumatic Diseases guidelines recommend that serum C3 and C4 levels should be measured in all suspected SLE cases, as low complement levels correlate with disease activity and major organ involvement 3, 6
• The American College of Rheumatology suggests that complete blood count (CBC) is essential for detecting cytopenias, such as anemia, leukopenia, lymphopenia, and thrombocytopenia, which correlate with disease activity and prognosis 3, 6
• The European League Against Rheumatism recommends that renal function assessment, including serum creatinine, urinalysis with microscopy, and quantification of proteinuria, should be performed to provide prognostic information for end-stage renal disease 3, 6

Testing Algorithm

• The Autoimmunity Reviews guidelines recommend a testing algorithm that starts with ANA screening, followed by anti-dsDNA, anti-ENA panel, complement levels, antiphospholipid antibodies, CBC, and renal function tests if ANA is positive 1, 4
• If ANA is negative but clinical suspicion remains high, anti-dsDNA testing and clinical follow-up are recommended, according to the European League Against Rheumatism guidelines 1