标题：Characterization of immune response in Cross-Reactive Immunological Material (CRIM)-positive infantile Pompe disease patients treated with enzyme replacement therapy
摘要：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 <51,200), similar to CRIM-negative patients. To date there has been no systematic study to analyze the extent of IgG antibody response in CRIM-positive IPD. Such data would be critical and could serve as a comparator group for potential immune modulation approaches. A retrospective analysis of the dataset from the original rhGAA clinical trials final reports was conducted. CRIM-positive patients who received ERT monotherapy and had >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.
关键词：Pompe disease ; Glycogen storage disease type II ; Neuromuscular disease ; Enzyme replacement therapy ; Anti-rhGAA Ig antibodies ; Antidrug antibodies ; IPD Infantile Pompe disease ; ERT Enzyme replacement therapy ; GAA Acid α-glucosidase ; GAA Gene encoding acid α-glucosidase ; rhGAA Recombinant human acid α-glucosidase ; CRIM Cross-reactive immunological material ; HSAT High and sustained antibody titers ; SIT Sustained intermediate titers ; LT Low titers ; LVMI Left ventricular mass index ; AIMS Alberta infant motor scale ; Glc4 Glucose tetrasaccharide ; EOW Every other week ; IgG Immunoglobulin G ; CI-MPR Cation-independent mannose 6-phosphate receptor ; RUSP Recommended universal screening panel ; HLA Human leukocyte antigen ; MHC Major histocompatibility complex ; iTEM Individualized T-cell epitope measure
