Abstract | BACKGROUND: METHODS: RESULTS: Median follow-up was 2.3 years. In blood, HS reached normal levels more frequently than DS (50% vs 12.5%, p=0.001), though normalization could take several years. DMBu normalized more rapidly than disaccharide levels in urine (p=0.02). Nineteen patients (83%) developed high antibody titers. Significant antibody-mediated inhibition of enzyme uptake was observed in 8 patients (35%), and this correlated strongly with a poorer biomarker response for HS and DS in blood and urine as well as for DMBu, DS:CS-ratio and HCII- T (all p<0.006). CONCLUSIONS: This study shows that, despite a response of all studied biomarkers to initiation of ERT, some biomarkers were less responsive than others, suggesting residual disease activity. In addition, the correlation of cellular uptake inhibitory antibodies with a decreased biomarker response demonstrates a functional role of these antibodies which may have important clinical consequences.
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Authors | Eveline J Langereis, Naomi van Vlies, Heather J Church, Ronald B Geskus, Carla E M Hollak, Simon A Jones, Wim Kulik, Henk van Lenthe, Jean Mercer, Lena Schreider, Karen L Tylee, Tom Wagemans, Frits A Wijburg, Brian W Bigger |
Journal | Molecular genetics and metabolism
(Mol Genet Metab)
Vol. 114
Issue 2
Pg. 129-37
(Feb 2015)
ISSN: 1096-7206 [Electronic] United States |
PMID | 25467058
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- Disaccharides
- Immunoglobulin G
- Recombinant Proteins
- Dermatan Sulfate
- Heparin Cofactor II
- Heparitin Sulfate
- Iduronidase
- Thrombin
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Topics |
- Adolescent
- Adult
- Biomarkers
(analysis)
- Child
- Child, Preschool
- Dermatan Sulfate
(analysis)
- Disaccharides
(analysis, blood, urine)
- Enzyme Replacement Therapy
- Female
- Follow-Up Studies
- Heparin Cofactor II
(analysis)
- Heparitin Sulfate
(analysis, blood, urine)
- Humans
- Iduronidase
(immunology, therapeutic use)
- Immunoglobulin G
(blood)
- Infant
- Infant, Newborn
- Male
- Mucopolysaccharidosis I
(blood, drug therapy, immunology, urine)
- Recombinant Proteins
(immunology, therapeutic use)
- Thrombin
(analysis)
- Young Adult
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