Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease.
PURPOSE: Gaucher disease is an exemplary orphan disorder. Enzyme replacement therapy with imiglucerase is effective, but very expensive. To improve the assessment of severity of disease and responses to this costly treatment, we have evaluated several enzymatic biomarkers and a newly-described chemokine. SUBJECTS AND METHODS: We studied 48 untreated adults with Type I Gaucher disease: 20 patients were studied after the introduction of enzyme replacement. Disease activity was monitored by serial measurement of platelet count, visceral volumes (spleen and liver) by magnetic resonance imaging, serum activities of total acid phosphatase, angiotensin-converting enzyme (ACE) and the lysosomal chitinase, chitotriosidase. Pulmonary and activation-regulated chemokine (PARC/CCL 18) was also determined in serum by ELISA. RESULTS: Serum PARC concentrations were elevated 10-40-fold in patients with Gaucher disease compared with 67 healthy controls, without overlap (P<0.0001). Unlike chitotriosidase, PARC was detectable in all individuals. Serum PARC was a reliable indicator of splenic (R=0.53, P<0.01) and liver (R=0.65, P<0.01) volume and platelet count (R=0.50, P<0.01). In splenectomized patients and in patients with null alleles of the chitotriosidase gene, serum PARC concentration correlates with visceral volume and other biomarkers of disease activity. Unlike chitotriosidase, serum PARC concentrations showed unbiased covariation with splenic and platelet responsiveness to enzyme replacement. CONCLUSION: Serum PARC concentrations are correlated with visceral Gaucher disease and with key clinical responses to enzyme complementation. Determination of this chemokine is a facile and universally applicable method that permits objective monitoring of enzyme replacement therapy for patients with Gaucher disease.