title: Limitations in quantitation of the biomarker CCL18 in Gaucher disease blood samples by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.
abstract: SELDI-TOF MS assisted the discovery of the chemokine CCL18/PARC as plasma biomarker for pathological storage cells in Gaucher disease patients. Prognostic elevation of CCL18 in blood of Gaucher patients has been confirmed by ELISA. Given its low molecular mass, positive charge, and relatively high abundance, CCL18 seems a particular attractive protein for SELDI-TOF based quantitation. Therefore, we determined CCL18 levels in plasma using SELDI-TOF MS and ELISA, in parallel. CCL18 levels in some blood samples were significantly underestimated when determined by SELDI-TOF MS. Spiking of recombinant CCL18 indicated that its detection by SELDI-TOF MS is strongly determined by the nature of the sample, even markedly varying between samples obtained from one donor at different time points. Independent of the total CCL18 concentration in blood only 1-10% of the chemokine bound to the ProteinChip Array. Even when comparable amounts of CCL18 from distinct samples were bound to the ProteinChip Array, diverse peak intensities could be observed. Thus, limited binding capacity and sample-dependent suppression of CCL18 ionization contribute significantly to the final peak intensity. In conclusion, SELDI-TOF MS offers no reliable procedure to quantitatively monitor CCL18 levels in blood and thus cannot be applied in evaluation of disease status of Gaucher patients.
authors.affiliation: Clinical Proteomics Facility, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands.
authors.forename: Mariëlle J
authors.initials: MJ
authors.lastname: van Breemen
authors.forename: Boris
authors.initials: B
authors.lastname: Bleijlevens
authors.forename: Chris G
authors.initials: CG
authors.lastname: de Koster
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D015415:Biomarkers / Q000097:blood; D019742:Chemokines, CC / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005776:Gaucher Disease / Q000097:blood*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D040081:Protein Array Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods* / Q000592:standards
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC