title: Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy.
abstract: To determine the effect of antibodies against recombinant human acid α-glucosidase (rhGAA) on treatment efficacy and safety, and to test whether the GAA genotype is involved in antibody formation.
  
  
  
  We used enzyme-linked immunosorbent assay (ELISA) to determine anti-rhGAA antibody titers at baseline and at 6, 12, and 36 months of rhGAA treatment. We measured the capacity of antibodies to neutralize rhGAA enzymatic activity or cellular uptake and the effects on infusion-associated reactions (IARs), muscle strength, and pulmonary function.
  
  
  
  Of 73 patients, 45 developed antibodies. Maximal titers were high (≥1:31,250) in 22% of patients, intermediate (1:1,250-1:31,250) in 40%, and none or low (0-1:1,250) in 38%. The common IVS1/delex18 GAA genotype was absent only in the high-titer group. The height of the titer positively correlated with the occurrence and number of IARs (P ≤ 0.001). On the group level, antibody titers did not correlate with treatment efficacy. Eight patients (11%) developed very high maximal titers (≥156,250), but only one patient showed high sustained neutralizing antibodies that probably interfered with treatment efficacy.
  
  
  
  In adults with Pompe disease, antibody formation does not interfere with rhGAA efficacy in the majority of patients, is associated with IARs, and may be attenuated by the IVS1/delex18 GAA genotype.Genet Med 19 1, 90-97.
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Juna M
authors.initials: JM
authors.lastname: de Vries
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Kuperus
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Molecular Stem Cell Biology, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Molecular Stem Cell Biology, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marian A
authors.initials: MA
authors.lastname: Kroos
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Stephan C A
authors.initials: SC
authors.lastname: Wens
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Molecular Stem Cell Biology, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Merel
authors.identifier: 0000-0002-6030-1820
authors.initials: M
authors.lastname: Stok
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nadine A M E
authors.initials: NA
authors.lastname: van der Beek
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kruijshaar
authors.affiliation: Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Molecular Stem Cell Biology, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: W W M Pim
authors.identifier: 0000-0002-7042-2482
authors.initials: WW
authors.lastname: Pijnappel
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D005260:Female; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D000520:alpha-Glucosidases / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; C509951:GAA protein, human; D000520:alpha-Glucosidases