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

Abstract

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 pharmacological substrate reduction reverses gpNMB abnormalities. In conclusion, gpNMB acts as a marker for glucosylceramide-laden macrophages in man and mouse and gpNMB should be considered as candidate biomarker for Gaucher disease in treatment monitoring.

• Authors: Gertjan Kramer, Wouter Wegdam, Wilma Donker-Koopman, Roelof Ottenhoff, Paulo Gaspar, Marri Verhoek, Jessica Nelson, Tanit Gabriel, Wouter Kallemeijn, Rolf G Boot, Jon D Laman, Johannes P C Vissers, Timothy Cox, Elena Pavlova, Mary Teresa Moran, Johannes M Aerts, Marco van Eijk
• Journal: FEBS open bio (FEBS Open Bio) Vol. 6 Issue 9 Pg. 902-13 (09 2016) ISSN: 2211-5463 [Print] England
• PMID: 27642553 (Publication Type: Journal Article)