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Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
PLoS One. 2012; 7(10):e47805.Plos

Abstract

INTRODUCTION

Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT.

METHODS

Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay.

RESULTS

Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke.

CONCLUSION

In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23094092

Citation

Rombach, Saskia M., et al. "Long-term Effect of Antibodies Against Infused Alpha-galactosidase a in Fabry Disease On Plasma and Urinary (lyso)Gb3 Reduction and Treatment Outcome." PloS One, vol. 7, no. 10, 2012, pp. e47805.
Rombach SM, Aerts JM, Poorthuis BJ, et al. Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome. PLoS One. 2012;7(10):e47805.
Rombach, S. M., Aerts, J. M., Poorthuis, B. J., Groener, J. E., Donker-Koopman, W., Hendriks, E., Mirzaian, M., Kuiper, S., Wijburg, F. A., Hollak, C. E., & Linthorst, G. E. (2012). Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome. PloS One, 7(10), e47805. https://doi.org/10.1371/journal.pone.0047805
Rombach SM, et al. Long-term Effect of Antibodies Against Infused Alpha-galactosidase a in Fabry Disease On Plasma and Urinary (lyso)Gb3 Reduction and Treatment Outcome. PLoS One. 2012;7(10):e47805. PubMed PMID: 23094092.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome. AU - Rombach,Saskia M, AU - Aerts,Johannes M F G, AU - Poorthuis,Ben J H M, AU - Groener,Johanna E M, AU - Donker-Koopman,Wilma, AU - Hendriks,Erik, AU - Mirzaian,Mina, AU - Kuiper,Sijmen, AU - Wijburg,Frits A, AU - Hollak,Carla E M, AU - Linthorst,Gabor E, Y1 - 2012/10/19/ PY - 2012/04/24/received PY - 2012/09/17/accepted PY - 2012/10/25/entrez PY - 2012/10/25/pubmed PY - 2013/4/2/medline SP - e47805 EP - e47805 JF - PloS one JO - PLoS One VL - 7 IS - 10 N2 - INTRODUCTION: Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT. METHODS: Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay. RESULTS: Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke. CONCLUSION: In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23094092/Long_term_effect_of_antibodies_against_infused_alpha_galactosidase_A_in_Fabry_disease_on_plasma_and_urinary__lyso_Gb3_reduction_and_treatment_outcome_ L2 - https://dx.plos.org/10.1371/journal.pone.0047805 DB - PRIME DP - Unbound Medicine ER -