Immune response to enzyme replacement therapy: Clinical signs of hypersensitivity reactions and altered enzyme distribution in a high titre rat model

Doug A. Brooks, John J. Hopwood, Barbara M. King

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Immune responses to enzyme replacement therapy (ERT) have been reported and can result in a hypersensitivity/anaphylactic reaction during or immediately after enzyme infusion. We have investigated the infusion of the lysosomal enzyme N-acetylgalactosamine 4-sulphatase (4-sulphatase) into immunized, high titre rats as a model of immune response to ERT. To simulate ERT, high and low titre rats were infused with different doses of radiolabelled recombinant human 4-sulphatase (3H-rh4S). There was evidence of altered targeting, inactivation and degradation of 4-sulphatase in high titre (titre 1 024 000) compared to low titre (titre 64) rats. There was more 4-sulphatase enzyme activity detected in 5 mg/kg high titre rats when compared to 1 mg/kg high titre rats, suggesting that the antibodies could be saturable in vivo. However, the rats treated with 5 mg/kg 3H-rh4S all had clinical signs of hypersensitivity reactions to 4-sulphatase infusion. There were no apparent signs of adverse reactions in either the high titre 1 mg/kg rats or the low titre rats (1, 5 mg/kg). The high titre 5 mg/kg rats also had changes in 3H-rh4S distribution, with lower levels delivered to the liver and a marked increase in the level remaining in plasma, when compared to either 1 mg/kg high titre rats or low titre rats (1, 5 mg/kg). Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2
Publication statusPublished or Issued - 14 Aug 1998


  • Antibody
  • Enzyme replacement therapy
  • Hypersensitivity
  • Immune reaction
  • Lysosomal storage disease
  • Treatment outcome

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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