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https://hdl.handle.net/2440/7030
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Type: | Journal article |
Title: | Immune response to enzyme replacement therapy: clinical signs of hypersensitivity reactions and altered enzyme distribution in a high titre rat model |
Author: | Brooks, D. Hopwood, J. King, B. |
Citation: | BBA: General Subjects, 1998; 1407(2):163-172 |
Publisher: | ELSEVIER SCIENCE BV |
Issue Date: | 1998 |
ISSN: | 0304-4165 1878-2434 |
Abstract: | 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 1024000) 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). |
Keywords: | Liver Animals Rats Metabolism, Inborn Errors Mucopolysaccharidosis VI Hypersensitivity Anaphylaxis Disease Models, Animal Sulfatases N-Acetylgalactosamine-4-Sulfatase Recombinant Proteins Centrifugation, Density Gradient Immunity |
DOI: | 10.1016/S0925-4439(98)00034-9 |
Published version: | http://dx.doi.org/10.1016/s0925-4439(98)00034-9 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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