Abstract | INTRODUCTION: 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 (pā=ā0.04). 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 | Saskia M Rombach, Johannes M F G Aerts, Ben J H M Poorthuis, Johanna E M Groener, Wilma Donker-Koopman, Erik Hendriks, Mina Mirzaian, Sijmen Kuiper, Frits A Wijburg, Carla E M Hollak, Gabor E Linthorst |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 10
Pg. e47805
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23094092
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies
- Globosides
- Glycolipids
- Sphingolipids
- Trihexosylceramides
- globotrihexosylceramide
- globotriaosyl lysosphingolipid
- alpha-Galactosidase
|
Topics |
- Adult
- Antibodies
(blood)
- Chromatography, High Pressure Liquid
- Chromatography, Liquid
- Enzyme Replacement Therapy
- Fabry Disease
(blood, drug therapy, immunology, urine)
- Female
- Globosides
(urine)
- Glycolipids
(blood)
- Humans
- Male
- Middle Aged
- Neutralization Tests
- Spectrometry, Mass, Electrospray Ionization
- Sphingolipids
(blood)
- Tandem Mass Spectrometry
- Time
- Treatment Outcome
- Trihexosylceramides
(urine)
- alpha-Galactosidase
(pharmacology, therapeutic use)
|