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.
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.
Authors: Rolf G Boot; Marri Verhoek; Mirjam Langeveld; G Herma Renkema; Carla E M Hollak; Jan J Weening; Wilma E Donker-Koopman; Johanna E Groener; Johannes M F G Aerts Journal: J Inherit Metab Dis Date: 2006-05-30 Impact factor: 4.982
Authors: Nick Dekker; Laura van Dussen; Carla E M Hollak; Herman Overkleeft; Saskia Scheij; Karen Ghauharali; Mariëlle J van Breemen; Maria J Ferraz; Johanna E M Groener; Mario Maas; Frits A Wijburg; Dave Speijer; Anna Tylki-Szymanska; Pramod K Mistry; Rolf G Boot; Johannes M Aerts Journal: Blood Date: 2011-08-25 Impact factor: 22.113
Authors: Vagishwari Murugesan; Wei-Lien Chuang; Jun Liu; Andrew Lischuk; Katherine Kacena; Haiqun Lin; Gregory M Pastores; Ruhua Yang; Joan Keutzer; Kate Zhang; Pramod K Mistry Journal: Am J Hematol Date: 2016-08-08 Impact factor: 10.047
Authors: Margaret M McGovern; Melissa P Wasserstein; Roberto Giugliani; Bruno Bembi; Marie T Vanier; Eugen Mengel; Scott E Brodie; David Mendelson; Gwen Skloot; Robert J Desnick; Noriko Kuriyama; Gerald F Cox Journal: Pediatrics Date: 2008-07-14 Impact factor: 7.124
Authors: Helena Hůlková; Helena Poupetová; Klaus Harzer; Pramod Mistry; Johannes M F G Aerts; Milan Elleder Journal: J Inherit Metab Dis Date: 2010-01-05 Impact factor: 4.982