Open AccessElevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models
Author(s) -
Kramer Gertjan,
Wegdam Wouter,
DonkerKoopman Wilma,
Ottenhoff Roelof,
Gaspar Paulo,
Verhoek Marri,
Nelson Jessica,
Gabriel Tanit,
Kallemeijn Wouter,
Boot Rolf G.,
Laman Jon D.,
Vissers Johannes P.C.,
Cox Timothy,
Pavlova Elena,
Moran Mary Teresa,
Aerts Johannes M.,
Eijk Marco
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12078
Subject(s) - glucocerebrosidase , gaucher's disease , glycoprotein , enzyme replacement therapy , biomarker , disease , medicine , substrate reduction therapy , proteome , ccl18 , lysosome , glucocerebroside , lysosomal storage disease , immunology , cancer research , biology , pathology , microbiology and biotechnology , enzyme , inflammation , bioinformatics , biochemistry , chemokine
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.