The Value of Anti-Drug Antibody Detection in Discriminating Patients from Healthy Controls and Predicting the Gross Motor Functional State in Patients with Pompe Disease.

内容摘要

Anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody formation is a major challenge in patients with Pompe disease receiving enzyme replacement therapy (ERT). The clinical significance of these antibodies and their detection methods remain uncertain. This study aimed to evaluate the diagnostic and functional relevance of anti-rhGAA antibodies in late-onset Pompe disease (LOPD) and to compare the performance of ELISA and Western blot assays. Fourteen patients with LOPD undergoing ERT and 14 age- and sex-matched healthy controls were studied. Serum anti-rhGAA antibodies and their IgG, IgM, and IgA isotypes were quantified using ELISA and verified by Western blot. Motor function was assessed using the Pompe Motor Function Levels Questionnaire, an adapted version of the GMFCS validated for Pompe disease. Total and isotype-specific anti-rhGAA antibody levels were significantly higher in patients than in controls. ROC analysis showed excellent discrimination between groups. Strong agreement was observed between ELISA and Western blot results. However, antibody levels were not significantly correlated with motor function grade. Given the small sample size (n = 14), this non-significant result may reflect limited statistical power rather than a true lack of association. Anti-rhGAA antibody detection effectively distinguishes LOPD patients from healthy individuals. Western blot provides a reliable, low-cost alternative to ELISA, particularly useful in resource-limited settings. Nevertheless, the prognostic utility of antibody titers for functional outcomes remains uncertain and warrants larger, multicenter validation studies.