Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency.

Abstract

Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185ng/ml (range 70-811ng/ml) and were increased compared to 10 healthy controls (median 36ng/ml, range 9-175ng/ml, p<0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109ng/ml, range 70-304ng/ml and 325ng/ml, range 165-811ng/ml, p<0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R=0.28, p=0.270; R=0.34, p=0.180; R=0.39, p=0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R=0.59, p=0.061, R=0.5, p=0.100, R=0.065, p=0.810, R=-0.38, p=0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort.