Antinuclear Antibody Interpretation: Patterns and Specificities

The clinician interprets antinuclear antibody (ANA) testing in the context of clinical presentation, understanding that ANA is a screening test with high sensitivity but low specificity for systemic autoimmune diseases. ANA is detected by indirect immunofluorescence (IIF) on HEp-2 cells -- the staining pattern provides diagnostic clues: homogeneous (associated with anti-dsDNA antibodies in SLE, anti-histone antibodies in drug-induced lupus), speckled (anti-Smith/anti-RNP in SLE, anti-SSA/SSB in Sjogren syndrome, anti-Scl-70 in systemic sclerosis), nucleolar (anti-RNA polymerase III in systemic sclerosis, anti-Th/To), and centromere (anti-centromere antibodies in limited cutaneous systemic sclerosis/CREST syndrome). ANA is positive in approximately 95% of SLE patients but also in 5-15% of healthy individuals (prevalence increases with age, female sex, and family history). The clinician orders ANA only when pre-test probability of autoimmune disease is adequate (clinical features suggesting SLE, systemic sclerosis, Sjogren syndrome, inflammatory myopathies) -- not as a routine screening test in the absence of clinical suspicion. A positive ANA requires reflex testing for specific antibodies to establish a diagnosis: anti-dsDNA and anti-Smith (specific for SLE), anti-SSA/Ro and anti-SSB/La (Sjogren syndrome, neonatal lupus), anti-Scl-70/topoisomerase I (diffuse systemic...