Contextual laboratory interpretation of anti-topoisomerase I positivity in systemic sclerosis: a de-duplicated real-world analysis

OBJECTIVES: To assess how routinely available serological findings contextualize anti-topoisomerase I positivity in systemic sclerosis (SSc). METHODS: We reanalyzed a single-center 2023 cohort using the earliest qualifying record per patient and strict recorded inpatient SSc diagnoses. Logistic models evaluated antibody signal intensity and antinuclear antibody (ANA) status, titer, and pattern. An available chemiluminescence immunoassay (CLIA) subset provided orthogonal analytical context. RESULTS: Among 669 patients with line-immunoassay (LIA) grayscale values >25 for anti-topoisomerase I, 440 were ANA-positive and 229 ANA-negative; SSc was recorded in 69/440 (15.7 %) and 2/229 (0.9 %), respectively. LIA intensity (per 10 units; OR 1.43, 95 % CI 1.30-1.58) and ANA positivity (OR 10.57, 95 % CI 2.51-44.57) were independently associated with recorded SSc. Adding ANA status increased AUC from 0.815 to 0.847 (p=0.011). Within ANA-positive patients, LIA intensity, ANA titer ≥1:160, and non-AC-29 pattern were independently informative; adding pattern increased AUC from 0.817 to 0.862 (p=0.011). In 268 CLIA observations, confirmation increased with LIA intensity; unadjusted rates were 74/122 (60.7 %) for ANA-positive and 61/146 (41.8 %) for ANA-negative observations (p=0.002). CONCLUSIONS: ANA status, LIA intensity, titer, and AC-29 provide complementary laboratory context for interpreting anti-topoisomerase I positivity.