Dataset Information

Elevated gpNMB in type 1 Gaucher disease patients

ABSTRACT: Gaucher disease (GD) is characterized by the presence of glucosylceramide-laden macrophages (Gaucher cells) as the result of deficiency in the lysosomal hydrolase glucocerebrosidase (GBA). Non-neuronopathic type 1 GD is effectively treated by infusions with macrophage-targeted recombinant glucocerebrosidase. We here report how LC-MSE analysis of the proteome of laser-dissected splenic Gaucher cells revealed high expression of several proteins amongst which was gpNMB. This was confirmed by histochemistry and RNA quantification. Macrophages produce gpNMB as membrane protein but release soluble fragments. In plasma of symptomatic Gaucher patients (n=59) soluble gpNMB was next found to be on average 25-fold increased prior to treatment, without overlap with control values, (control mean: 20 ng/ml; range 11-34 ng/ml vs. GD mean: 495 ng/ml; range: 137-1283 ng/ml).

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Spleen, Macrophage

DISEASE(S): Gaucher's Disease

SUBMITTER: Gertjan Kramer

LAB HEAD: J.M.F.G. Aerts

PROVIDER: PXD001598 | Pride | 2016-09-27

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	121108_D2_028.raw.zip	Raw
	121108_D2_028_20141210154822.zip	Other
	121108_D2_029.raw.zip	Raw
	121108_D2_029_20141210160200.zip	Other
	121108_D2_030.raw.zip	Raw

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Publications

Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models.

Kramer Gertjan G Wegdam Wouter W Donker-Koopman Wilma W Ottenhoff Roelof R Gaspar Paulo P Verhoek Marri M Nelson Jessica J Gabriel Tanit T Kallemeijn Wouter W Boot Rolf G RG Laman Jon D JD Vissers Johannes P C JP Cox Timothy T Pavlova Elena E Moran Mary Teresa MT Aerts Johannes M JM van Eijk Marco M

FEBS open bio 20160730 9

Gaucher disease is caused by inherited deficiency of lysosomal glucocerebrosidase. Proteome analysis of laser-dissected splenic Gaucher cells revealed increased amounts of glycoprotein nonmetastatic melanoma protein B (gpNMB). Plasma gpNMB was also elevated, correlating with chitotriosidase and CCL18, which are established markers for human Gaucher cells. In Gaucher mice, gpNMB is also produced by Gaucher cells. Correction of glucocerebrosidase deficiency in mice by gene transfer or pharmacologi ...[more]

PMID: 27642553

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