Potential biomarkers of osteonecrosis in Gaucher disease
| Autor: | Elena Pavlova, D Hughes, Ian G. McFarlane, Atul Mehta, J. Edmond Wraith, Jane Tindall, Timothy M. Cox, Patrick Deegan |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Imiglucerase Adolescent Gastroenterology CCL5 Young Adult Internal medicine Medicine Humans Enzyme Replacement Therapy Young adult Molecular Biology Aged Aged 80 and over Hematology Gaucher Disease business.industry CCL18 Case-control study Osteonecrosis Cell Biology Enzyme replacement therapy Middle Aged Up-Regulation Hexosaminidases Case-Control Studies Chemokines CC Immunology Molecular Medicine Cytokines Female business Complication Biomarkers medicine.drug |
| Zdroj: | Blood cells, moleculesdiseases. 46(1) |
| ISSN: | 1096-0961 |
| Popis: | To investigate the relationship between chemokines and cytokines and osteonecrosis in Gaucher disease, we conducted multiplex assays in a cohort of 100 adult patients.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.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 (p0.05 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, p0.05). 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, p0.05). Treatment exposures were similar.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. |
| Databáze: | OpenAIRE |
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