Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.

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

doi:10.1016/j.ymgme.2014.10.012

Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.

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

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Antibody formation can interfere with effects of enzyme replacement therapy (ERT) in lysosomal storage diseases. Biomarkers are used as surrogate marker for disease burden in MPS I, but large systematic studies evaluating the response of biomarkers to ERT are lacking. We, for the first time, investigated the response of a large panel of biomarkers to long term ERT in MPS I patients and correlate these responses with antibody formation and antibody mediated cellular uptake inhibition. METHODS: A total of 428 blood and urine samples were collected during long-term ERT in 24 MPS I patients and an extensive set of biomarkers was analyzed, including heparan sulfate (HS) and dermatan sulfate (DS) derived disaccharides; total urinary GAGs (DMBu); urinary DS:CS ratio and serum heparin co-factor II thrombin levels (HCII-T). IgG antibody titers and the effect of antibodies on cellular uptake of the enzyme were determined for 23 patients. 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

Original language	English
Journal	Molecular genetics and metabolism
Volume	114
Issue number	2
DOIs	https://doi.org/10.1016/j.ymgme.2014.10.012
Publication status	Published - Feb 2015

Keywords

Antibody formation
Biomarker
Enzyme replacement therapy
Glycosaminoglycans
Laronidase
Mucopolysaccharidosis type I

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10.1016/j.ymgme.2014.10.012

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Langereis, E. J., van Vlies, N., Church, H. J., Geskus, R. B., Hollak, C. E. M., Jones, S. A., Kulik, W., van Lenthe, H., Mercer, J., Schreider, L., Tylee, K. L., Wagemans, T., Wijburg, F. A., & Bigger, B. W. (2015). Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy. Molecular genetics and metabolism, 114(2). https://doi.org/10.1016/j.ymgme.2014.10.012

@article{92b19a40877b427580f734db002294d9,

title = "Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.",

abstract = "BACKGROUND: Antibody formation can interfere with effects of enzyme replacement therapy (ERT) in lysosomal storage diseases. Biomarkers are used as surrogate marker for disease burden in MPS I, but large systematic studies evaluating the response of biomarkers to ERT are lacking. We, for the first time, investigated the response of a large panel of biomarkers to long term ERT in MPS I patients and correlate these responses with antibody formation and antibody mediated cellular uptake inhibition. METHODS: A total of 428 blood and urine samples were collected during long-term ERT in 24 MPS I patients and an extensive set of biomarkers was analyzed, including heparan sulfate (HS) and dermatan sulfate (DS) derived disaccharides; total urinary GAGs (DMBu); urinary DS:CS ratio and serum heparin co-factor II thrombin levels (HCII-T). IgG antibody titers and the effect of antibodies on cellular uptake of the enzyme were determined for 23 patients. 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",

keywords = "Antibody formation, Biomarker, Enzyme replacement therapy, Glycosaminoglycans, Laronidase, Mucopolysaccharidosis type I",

author = "Langereis, {Eveline J} and {van Vlies}, Naomi and Church, {Heather J} and Geskus, {Ronald B} and Hollak, {Carla E M} and Jones, {Simon A} and Wim Kulik and {van Lenthe}, Henk and Jean Mercer and Lena Schreider and Tylee, {Karen L} and Tom Wagemans and Wijburg, {Frits A} and Bigger, {Brian W}",

year = "2015",

month = feb,

doi = "10.1016/j.ymgme.2014.10.012",

language = "English",

volume = "114",

journal = "Molecular genetics and metabolism",

issn = "1096-7206",

publisher = "Elsevier BV",

number = "2",

}

Langereis, EJ, van Vlies, N, Church, HJ, Geskus, RB, Hollak, CEM, Jones, SA, Kulik, W, van Lenthe, H, Mercer, J, Schreider, L, Tylee, KL, Wagemans, T, Wijburg, FA & Bigger, BW 2015, 'Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.', Molecular genetics and metabolism, vol. 114, no. 2. https://doi.org/10.1016/j.ymgme.2014.10.012

TY - JOUR

T1 - Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.

AU - Langereis, Eveline J

AU - van Vlies, Naomi

AU - Church, Heather J

AU - Geskus, Ronald B

AU - Hollak, Carla E M

AU - Jones, Simon A

AU - Kulik, Wim

AU - van Lenthe, Henk

AU - Mercer, Jean

AU - Schreider, Lena

AU - Tylee, Karen L

AU - Wagemans, Tom

AU - Wijburg, Frits A

AU - Bigger, Brian W

PY - 2015/2

Y1 - 2015/2

N2 - BACKGROUND: Antibody formation can interfere with effects of enzyme replacement therapy (ERT) in lysosomal storage diseases. Biomarkers are used as surrogate marker for disease burden in MPS I, but large systematic studies evaluating the response of biomarkers to ERT are lacking. We, for the first time, investigated the response of a large panel of biomarkers to long term ERT in MPS I patients and correlate these responses with antibody formation and antibody mediated cellular uptake inhibition. METHODS: A total of 428 blood and urine samples were collected during long-term ERT in 24 MPS I patients and an extensive set of biomarkers was analyzed, including heparan sulfate (HS) and dermatan sulfate (DS) derived disaccharides; total urinary GAGs (DMBu); urinary DS:CS ratio and serum heparin co-factor II thrombin levels (HCII-T). IgG antibody titers and the effect of antibodies on cellular uptake of the enzyme were determined for 23 patients. 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

AB - BACKGROUND: Antibody formation can interfere with effects of enzyme replacement therapy (ERT) in lysosomal storage diseases. Biomarkers are used as surrogate marker for disease burden in MPS I, but large systematic studies evaluating the response of biomarkers to ERT are lacking. We, for the first time, investigated the response of a large panel of biomarkers to long term ERT in MPS I patients and correlate these responses with antibody formation and antibody mediated cellular uptake inhibition. METHODS: A total of 428 blood and urine samples were collected during long-term ERT in 24 MPS I patients and an extensive set of biomarkers was analyzed, including heparan sulfate (HS) and dermatan sulfate (DS) derived disaccharides; total urinary GAGs (DMBu); urinary DS:CS ratio and serum heparin co-factor II thrombin levels (HCII-T). IgG antibody titers and the effect of antibodies on cellular uptake of the enzyme were determined for 23 patients. 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

KW - Antibody formation

KW - Biomarker

KW - Enzyme replacement therapy

KW - Glycosaminoglycans

KW - Laronidase

KW - Mucopolysaccharidosis type I

U2 - 10.1016/j.ymgme.2014.10.012

DO - 10.1016/j.ymgme.2014.10.012

M3 - Article

C2 - 25467058

SN - 1096-7206

VL - 114

JO - Molecular genetics and metabolism

JF - Molecular genetics and metabolism

IS - 2

ER -

Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.

Abstract

Keywords

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