title: Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.
abstract: OBJECTIVE
  Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT).
  
  
  METHODS
  Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin.
  
  
  RESULTS
  Neopterin levels were significantly increased in treatment-naïve patients (mean 11.90 ± 5.82 nM) compared with controls (6.63 ± 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 ± 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778.
  
  
  CONCLUSIONS
  Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder.
  
  
  CONCLUSIONS
  Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients.
authors.affiliation: a Department of Medical Biochemistry , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Cristina
authors.initials: C
authors.lastname: Drugan
authors.affiliation: b Department of Medical Informatics and Biostatistics , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Tudor C
authors.initials: TC
authors.lastname: Drugan
authors.affiliation: c Department of Clinical Immunology , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Nicolae
authors.initials: N
authors.lastname: Miron
authors.affiliation: d Department of Paediatrics, Paediatric Clinic I , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Paula
authors.initials: P
authors.lastname: Grigorescu-Sido
authors.affiliation: d Department of Paediatrics, Paediatric Clinic I , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Naşcu
authors.affiliation: a Department of Medical Biochemistry , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cătană
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005776:Gaucher Disease / Q000097:blood*; D006801:Humans; D008297:Male; D019798:Neopterin / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019798:Neopterin
keywords: Biomarkers; Chitotriosidase; Gaucher disease; Macrophage activation; Neopterin