Characterization of immune response in Cross-Reactive Immunological Material (CRIM)-positive infantile Pompe disease patients treated with enzyme replacement therapy

Abstract

Enzyme replacement therapy (ERT) with rhGAA has improved clinical outcomes in infantile Pompe disease (IPD). A subset of CRIM-positive IPD patients develop high and sustained antibody titers (HSAT; ≥51,200) and/or sustained intermediate titer (SIT; ≥12,800 and 6 months of antibody titer data available, were included in the study. Patients were classified based on their longitudinal antibody titers into HSAT, SIT, and low titer (LT; <12,800) groups. Of the 37 patients that met inclusion criteria, five (13%), seven (19%), and 25 (68%) developed HSAT, SIT, and LT, respectively. Median peak titers were 204,800 (51,200–409,600), 25,600 (12,800–51,200), and 800 (200–12,800) for HSAT, SIT, and LT groups, respectively. Median last titers were 102,400 (51,200–409,600), 1600 (200–25,600), and 400 (0–12,800) at median time since ERT initiation of 94 weeks (64–155 weeks), 104 weeks (86–144 weeks), and 130 weeks (38–182 weeks) for HSAT, SIT, and LT groups, respectively. 32% (12/37) of CRIM-positive IPD patients developed HSAT/SIT which may lead to limited ERT response and clinical decline. Further Studies are needed to identify CRIM-positive IPD patients at risk of developing HSAT/SIT, especially with the addition of Pompe disease to the newborn screening. Keywords: Pompe disease, Glycogen storage disease type II, Neuromuscular disease, Enzyme replacement therapy, Anti-rhGAA Ig antibodies, Antidrug antibodies