The Effect of Anti‐Scl‐70 Antibody Determination Method on Its Predictive Significance for Interstitial Lung Disease Progression in Systemic Sclerosis

OBJECTIVE: The objective of this study was to assess the predictive significance of anti‐Scl‐70 (anti‐topoisomerase I) antibodies, as determined by three different methods, for decline in forced vital capacity (FVC) within the first year of follow‐up in patients with systemic sclerosis (SSc)‐related interstitial lung disease (ILD). METHODS: Patients in the Genetics Versus Environment in Scleroderma Outcome Study cohort who had ILD (verified by imaging) and available FVC% at enrollment, plus 12 to 18 months thereafter, were examined. All patients had a disease duration of 5 years or less at enrollment. The annualized percentage change in FVC% at 1 year follow‐up was the outcome variable. Anti‐Scl‐70 antibodies were determined by passive immunodiffusion (ID) against calf thymus extract, chemiluminescent immunoassay (CIA), and line blot immunoassay (LIA). RESULTS: Ninety‐one patients with a mean disease duration of 2.36 years were included. Anti‐Scl‐70 antibodies by ID predicted a faster rate of FVC% decline (b = −0.06, P = 0.04). None of the other clinical or serological variables significantly predicted ILD progression. Interestingly, anti‐Scl‐70 antibodies as determined by CIA and LIA were not significant predictors of FVC decline (P = 0.26 and 0.64, respectively). The observed level of agreement between ID and LIA was moderate (κ = 0.568), whereas it was good between ID and CIA (κ = 0.66). CONCLUSION: Anti‐Scl‐70 antibodies determined by ID predicted faster FVC decline in patients with SSc‐related ILD. Notably, both CIA and LIA for the same antibody did not predict rate of FVC decline at their current cutoffs of positivity. The discrepancy observed between anti‐Scl‐70 antibody assays can have relevant implications for clinical care and trial enrichment strategies in SSc‐ILD.