Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention
Open Access
- 1 January 2004
- journal article
- Published by American Society of Hematology in Blood
- Vol. 103 (1), 33-39
- https://doi.org/10.1182/blood-2003-05-1612
Abstract
Gaucher disease is characterized by storage of glucosylceramide in lysosomes of tissue macrophages as the result of an autosomal recessively inherited deficiency in glucocerebrosidase. Progressive accumulation of these glycolipid-laden Gaucher cells causes a variety of debilitating symptoms. The disease can be effectively treated by costly intravenous infusions with recombinant glucocerebrosidase. Chitotriosidase is massively secreted by Gaucher cells and its plasma levels are used to monitor efficacy of enzyme therapy. Broad-scale application is hampered by the common genetic defect in this surrogate marker. We report that in plasma of symptomatic patients with Gaucher disease the chemokine CCL18 is on average 29-fold elevated, without overlap between patient and control values (median control plasma level is 33 ng/mL, range, 10-72 ng/mL; median Gaucher plasma level is 948 ng/mL, range, 237-2285 ng/mL). Plasma CCL18 concentrations decrease during therapy, comparably to chitotriosidase levels. Immunohistochemistry demonstrates that Gaucher cells are the prominent source of CCL18. Plasma CCL18 levels can serve as alternative surrogate marker for storage cells in patients with Gaucher disease and monitoring of plasma CCL18 levels proves to be useful in determination of therapeutic efficacy, especially in patients who are deficient in chitotriosidase activity. The potential physiologic consequences of chronically elevated CCL18 in patients with Gaucher disease are discussed.Keywords
This publication has 35 references indexed in Scilit:
- Identification of full, partial and inverse CC chemokine receptor 3 agonists using [35S]GTPγS bindingEuropean Journal of Pharmacology, 2002
- Identification of Biologically Active Chemokine Isoforms from Ascitic Fluid and Elevated Levels of CCL18/Pulmonary and Activation-regulated Chemokine in Ovarian CarcinomaPublished by Elsevier BV ,2002
- Dixon Quantitative Chemical Shift Imaging Is a Sensitive Tool for the Evaluation of Bone Marrow Responses to Individualized Doses of Enzyme Supplementation Therapy in Type 1 Gaucher DiseaseBlood Cells, Molecules, and Diseases, 2001
- The Biology of Chemokines and their ReceptorsAnnual Review of Immunology, 2000
- Expression and Cellular Localization of the CC Chemokines PARC and ELC in Human Atherosclerotic PlaquesThe American Journal of Pathology, 1999
- Detection of human cytokines in situ using antibody and probe based methodsJournal of Immunological Methods, 1995
- Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease.JCI Insight, 1994
- Correction of neutrophil chemotaxis defect in patients with gaucher disease by low‐dose enzyme replacement therapyAmerican Journal of Hematology, 1993
- Abnormal neutrophil chemotaxis in Gaucher diseaseBritish Journal of Haematology, 1993
- Gaucher DiseaseMedicine, 1992