title: Potential biomarkers of osteonecrosis in Gaucher disease.
abstract: BACKGROUND
  To investigate the relationship between chemokines and cytokines and osteonecrosis in Gaucher disease, we conducted multiplex assays in a cohort of 100 adult patients.
  
  
  METHODS
  Mean age was 45 years (18-86); 92 Gaucher patients received imiglucerase (median duration 8 years (2-18)). Forty-three had experienced osteonecrosis (ON), and eight had ON despite enzyme therapy. Serum cytokines/chemokines were determined by fluorimetric bead arrays in samples from Gaucher patients and healthy volunteers (10 males and 10 females). Intra-assay and inter-assay coefficients of variation were 2%-9.8% and 5.6%-15%, respectively.
  
  
  RESULTS
  VEGF and CCL5/RANTES did not differ between Gaucher and control samples. Concentrations of CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL8/IL-8, IL-1ra and CCL18/PARC were elevated in Gaucher patients (p<0.05 for each). Median CCL4/MIP-1β, CXCL8/IL-8, CCL5/RANTES and CCL18/PARC concentrations were greater in the 43 osteonecrosis patients (88.6 pg/mL, 30.5 pg/mL, 89.6 ng/mL and 434 ng/mL, respectively) compared with the 57 patients who had no evidence of osteonecrosis (medians of 59.4, 13.3, 62.7 and 283, respectively, p<0.05). Moreover, the eight patients with ON despite imiglucerase had median concentrations of CCL3/MIP-1α, CCL4/MIP-1β, CXCL8/IL-8, CCL5/RANTES and CCL18/PARC (73.2, 120.9, 36.3 pg/mL, 105 and 767 ng/mL, respectively), which significantly exceeded the values in 84 patients now free of ON (52.3, 71.2, 16.5 pg/mL, 69.5 and 315 ng/mL, respectively, p<0.05). Treatment exposures were similar.
  
  
  CONCLUSIONS
  Numerous serum cytokines are elevated in Gaucher disease. CCL18/PARC, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES and CXCL8/IL-8 are potential biomarkers of osteonecrosis and may allow prediction of this disabling complication.
authors.affiliation: Department of Medicine, University of Cambridge, UK. ep316@medschl.cam.ac.uk
authors.forename: Elena V
authors.initials: EV
authors.lastname: Pavlova
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Deegan
authors.forename: Jane
authors.initials: J
authors.lastname: Tindall
authors.forename: Ian
authors.initials: I
authors.lastname: McFarlane
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.forename: Derralyn
authors.initials: D
authors.lastname: Hughes
authors.forename: J Edmond
authors.initials: JE
authors.lastname: Wraith
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000097:blood; D016207:Cytokines / Q000097:blood*; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000097:blood* / Q000150:complications*; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D006596:Hexosaminidases; C086400:chitotriosidase