title: 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.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands; European Molecular Biology Laboratory Germany.
authors.forename: Gertjan
authors.initials: G
authors.lastname: Kramer
authors.affiliation: Department of Gynecology Academic Medical Center Amsterdam The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Wegdam
authors.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Donker-Koopman
authors.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands.
authors.forename: Roelof
authors.initials: R
authors.lastname: Ottenhoff
authors.affiliation: Organelle Biogenesis & Function Group Instituto de Investigação e Inovação em Saúde (I3S) Porto Portugal; Institute of Molecular and Cell Biology (IBMC) Universidade do Porto Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS) Universidade do Porto Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Gaspar
authors.affiliation: Department of Medical Biochemistry Leiden Institute of Chemistry Leiden University The Netherlands.
authors.forename: Marri
authors.initials: M
authors.lastname: Verhoek
authors.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nelson
authors.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands.
authors.forename: Tanit
authors.initials: T
authors.lastname: Gabriel
authors.affiliation: Department of Medical Biochemistry Leiden Institute of Chemistry Leiden University The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Kallemeijn
authors.affiliation: Department of Medical Biochemistry Leiden Institute of Chemistry Leiden University The Netherlands.
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.affiliation: Department of Neuroscience University Medical Center Groningen The Netherlands.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: Waters Corporation Wilmslow UK.
authors.forename: Johannes P C
authors.initials: JP
authors.lastname: Vissers
authors.affiliation: Department of Internal Medicine Addenbrooke's Hospital Cambridge UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cox
authors.affiliation: Department of Internal Medicine Addenbrooke's Hospital Cambridge UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Pavlova
authors.affiliation: Department of Internal Medicine Addenbrooke's Hospital Cambridge UK.
authors.forename: Mary Teresa
authors.initials: MT
authors.lastname: Moran
authors.affiliation: Department of Medical Biochemistry Leiden Institute of Chemistry Leiden University The Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.affiliation: Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands; Department of Medical Biochemistry Leiden Institute of Chemistry Leiden University The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van Eijk
keywords: DC‐HIL; chitotriosidase; glucosylceramide; lysosome; osteoactivin; storage disease