cdw17-antigen and Gaucher-Disease

Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.

Topics: Antigens, CD; Autoimmune Diseases; Autophagy; Calcium; Endoplasmic Reticulum; Free Radicals; G(M2) Ganglioside; G(M3) Ganglioside; Gaucher Disease; Humans; Lactosylceramides; Lysosomal Storage Diseases; Lysosomes; Mitochondria; Oxidative Stress

Gaucher disease is a lysosomal storage disorder characterized by a deficiency of the enzyme acid beta-glucosidase. The clinical manifestations of Gaucher disease are highly variable, and although certain genotypes are often associated with mild or severe symptoms, a defined correlation between genotype and phenotype does not exist. Identification of biochemical markers characteristic of pathology may be of use in predicting the progression of the disease state. In this study the relationship among genotype, glycolipid substrates, lysosomal proteins, and the clinical manifestations of Gaucher disease has been evaluated. Plasma glycolipids were analyzed using electrospray ionization-tandem mass spectrometry. Lysosomal-associated membrane protein-1 (LAMP-1) and saposin C were determined by immunoquantification. Patients with Gaucher disease were shown to have an increased 16:0-glucosylceramide/16:0-lactosylceramide ratio and elevated concentrations of LAMP-1 and saposin C in plasma. A general relationship was found to exist among the 16:0-glucosylceramide/16:0-lactosylceramide ratio, LAMP-1 and saposin C levels, and patient phenotype, providing a refinement of the genotype-phenotype correlation. These findings have major implications for the diagnosis, prediction of disease severity, and monitoring of therapy in patients with Gaucher disease.

Topics: Adolescent; Adult; Antigens, CD; Biomarkers; Child; Child, Preschool; Disease Progression; Female; Gaucher Disease; Genotype; Glucosylceramides; Glycoproteins; Humans; Infant; Lactosylceramides; Lysosomal Membrane Proteins; Male; Membrane Glycoproteins; Middle Aged; Phenotype; Predictive Value of Tests; Saposins

Topics: Animals; Antigens, CD; Brain Chemistry; Cerebrosides; Chromatography, Thin Layer; Erythrocytes; Fabry Disease; Galactosylceramides; Gaucher Disease; Glucosylceramides; Glycosphingolipids; Humans; Kidney; Lactosylceramides; Swine