Quantification of Anti‐Ro52, Anti‐Ro60 and Anti‐La Autoantibodies at High Sample Dilution and Their Predictive Value for Congenital Heart Block

ABSTRACT

Maternal anti‐Ro/La antibodies confer a risk of congenital heart block (CHB), but current methods for predicting risk relying on the presence or absence of these autoantibodies perform poorly. To identify more accurate biomarkers of CHB risk, we investigated the association between maternal levels of autoantibodies and the risk of CHB. A total of 318 women positive for anti‐Ro/SSA autoantibodies were included. Autoantibody presence was obtained from health records for all, and ELISA was used to quantify levels of anti‐Ro52, anti‐Ro60, and anti‐La in a subset of 116 women with samples obtained during pregnancy, including 27 CHB‐affected pregnancies. Predictive models for CHB risk were developed using logistic regression and machine learning. Anti‐Ro/SSA positive women with anti‐Ro60 were more likely to have pregnancies with CHB ( p  < 0.05). Levels of both anti‐Ro60 ( p  < 0.001) and anti‐Ro52 ( p  < 0.05) were significantly higher in CHB‐affected pregnancies and correlated ( r  = 0.8, p  < 0.0001), while levels of anti‐La did not differ between groups. Levels of anti‐Ro60 were identified as the strongest individual predictor of CHB, with a relative risk of 16.3 (95% CI 1.04–255.0, p  < 0.001) for the top versus the bottom decile. In all tested combinations, models that included anti‐Ro60 levels outperformed models that did not. Models based on anti‐Ro60 levels alone reached an area under the curve (AUC) of 0.76 and an odds ratio (OR) per standard deviation increase of 2.8 (95% CI 1.6–5.3). These findings confirm a strong association between maternal anti‐Ro antibody levels and CHB risk in anti‐SSA‐positive pregnancy, highlighting anti‐Ro60 autoantibody levels as a valuable biomarker in risk stratification.