Abstract:
:Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes of tissue macrophages (Gaucher cells). Here we show glucosylsphingosine, the deacylated form of glucosylceramide, to be markedly increased in plasma of symptomatic nonneuronopathic (type 1) Gaucher patients (n = 64, median = 230.7 nM, range 15.6-1035.2 nM; normal (n = 28): median 1.3 nM, range 0.8-2.7 nM). The method developed for mass spectrometric quantification of plasma glucosylsphingosine is sensitive and robust. Plasma glucosylsphingosine levels correlate with established plasma markers of Gaucher cells, chitotriosidase (ρ = 0.66) and CCL18 (ρ = 0.40). Treatment of Gaucher disease patients by supplementing macrophages with mannose-receptor targeted recombinant glucocerebrosidase results in glucosylsphingosine reduction, similar to protein markers of Gaucher cells. Since macrophages prominently accumulate the lysoglycosphingolipid on glucocerebrosidase inactivation, Gaucher cells seem a major source of the elevated plasma glucosylsphingosine. Our findings show that plasma glucosylsphingosine can qualify as a biomarker for type 1 Gaucher disease, but that further investigations are warranted regarding its relationship with clinical manifestations of Gaucher disease.
journal_name
Bloodjournal_title
Bloodauthors
Dekker N,van Dussen L,Hollak CE,Overkleeft H,Scheij S,Ghauharali K,van Breemen MJ,Ferraz MJ,Groener JE,Maas M,Wijburg FA,Speijer D,Tylki-Szymanska A,Mistry PK,Boot RG,Aerts JMdoi
10.1182/blood-2011-05-352971subject
Has Abstractpub_date
2011-10-20 00:00:00pages
e118-27issue
16eissn
0006-4971issn
1528-0020pii
blood-2011-05-352971journal_volume
118pub_type
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