Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention

Blood. 2004 Jan 1;103(1):33-9. doi: 10.1182/blood-2003-05-1612. Epub 2003 Sep 11.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokines, CC / blood*
  • Child
  • Female
  • Gaucher Disease / blood*
  • Gaucher Disease / immunology
  • Gaucher Disease / therapy
  • Glucosylceramidase / therapeutic use
  • Hexosaminidases / blood
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / therapeutic use

Substances

  • Biomarkers
  • CCL18 protein, human
  • Chemokines, CC
  • Recombinant Proteins
  • Hexosaminidases
  • chitotriosidase
  • Glucosylceramidase