FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2550116984> ?p ?o ?g. }

• W2550116984 abstract "Abstract Abstract 1102 Introduction: Gaucher disease (GD) is due to an inborn deficiency of glucocerebrosidase (GC), that leads to the accumulation of glucosylceramide in monocytes/macrophages, known as “Gaucher cells”, which are thought to be responsible for a wide range of symptoms. Imiglucerase (CEREZYME®, Genzyme Corporation) (IMI) is the first line treatment of type 1 GD patients. Two new biosimilar agents, velaglucerase-alfa (VPRIV®, Shire Human Genetic Therapies, Dublin, Ireland) (VEL) and taliglucerase-alfa (PROTALIX®, Biotherapeutics, Pfizer) (TAL), have been described as being similar to IMI but differing slightly in glycan structure which could have an impact on macrophage uptake and thus on therapeutic efficacy. However, the ability of native GD cells to capture recombinant enzymes (REs) remains unknown. We used blood monocytes (Mo) from GD patients and healthy donors (HD) as a model to compare the uptake of the three REs. Patients and methods: After informed consent was obtained, cells were obtained from healthy donor blood (n=34). The left over part of biological samples collected for routine analysis from Gaucher patients (n=6) could be used for research because patients had been informed and did not verbally express any disagreement. Mononuclear cells were incubated with three concentrations of each RE (0.1, 0.5 and 1 U/ml) at 37°C for 30 minutes and one hour and washed twice with PBS to eliminate exogenous RE before evaluation of intra-cellular GC activity by standardized flow cytometry as previously described (Berger J. et al., Br J Haematol 2010) Results: Firstly, we confirmed that GD Mo (n=6) showed a marked enzyme deficiency (about 7% of the normal endogenous activity) as compared to normal glucocerebrosidase activity (GCA) (n=34) Then we observed a dose-dependent in vitro uptake of IMI, TAL and VEL in Mo from 4 untreated GD patients. However, the intra-monocyte (IMo) GCA of TAL was systematically lower than that of IMI and VEL. Case analysis showed an inter-patient heterogeneity, with the highest increase of intra-monocyte enzyme activity for all REs in patient #2 and the lowest in patient #3; this observation was confirmed in vivo by analysis of Mo 15 min. after the end of the first IMI infusion (× 38 and × 9 endogeneous IMoGCA respectively) whereas patient #2 had received a lower dose of enzyme (45 U/kg/2 weeks vs 60 U/kg/2 weeks). Interestingly, patient #2 showed mild GD suffering only thrombocytopenia and asthenia while patient #3 had an aggressive form of GD, with bone disorders (aseptic osteonecrosis, bone infarction and pseudarthrosis after traumatic fracture). Patient #2 responded rapidly, with improved thrombocytopenia (68%) and increased hemoglobin level (+1.9g/dL) from M3 but hematological response for patient #3 could not be evaluated because initial parameters had been normal in this patient who had been splenectomized 20 years ago. Because of the chitotriosidase deficiency of patient #2, we used plasma CCL18 as a biomarker; its kinetic of decrease was clearly more rapid than for patient #3. Similarly, correction of glycosylated-ferritin was better than in patient #2. The two other patients with IMoGCA values close to that of patient #2 had non-progressive disease not requiring treatment (patient #1), or had thrombocytopenia that improved over the expected period of time (patient #4). Discussion: In conclusion, this study shows inter-patient variability in the ability of blood Mo to store recombinant enzymes which to our knowledge has not been previously reported. This was confirmed in vivo 15 min. after the start of the infusion. This variability could partially explain the heterogeneity of GD response to enzyme replacement therapy. In this small series, the least aggressive disease corresponded to the highest intra-monocyte GCA and the most aggressive disease to the least intra-monocyte GCA. Six-month follow-up showed differences in change in biological biomarkers suggesting a relationship between intra-monocyte GCA and disease response. Furthermore in this in vitro GD Mo model, all the compounds available are not similar, even if their chemical structures are only slightly different with no relationship with the expression of the CD206 (data not shown). Another RE influx mechanism could exist and influence enzyme replacement therapy. These findings could help in customizing replacement therapy. Disclosures: Belmatoug: Genzyme: Consultancy; Shire: Research Funding. Berger:Shire: Consultancy; Genzyme: Consultancy, Research Funding." @default.
• W2550116984 created "2016-11-30" @default.
• W2550116984 creator A5019566537 @default.
• W2550116984 creator A5032207811 @default.
• W2550116984 creator A5042547987 @default.
• W2550116984 creator A5045981135 @default.
• W2550116984 creator A5055335263 @default.
• W2550116984 creator A5060887030 @default.
• W2550116984 creator A5061164405 @default.
• W2550116984 creator A5069537100 @default.
• W2550116984 creator A5080749717 @default.
• W2550116984 creator A5087192702 @default.
• W2550116984 date "2011-11-18" @default.
• W2550116984 modified "2023-09-27" @default.
• W2550116984 title "The Uptake of Recombinant Glucocerebrosidases by Blood Monocytes From Type 1 Gaucher Disease Patients Is Heterogeneous" @default.
• W2550116984 doi "https://doi.org/10.1182/blood.v118.21.1102.1102" @default.
• W2550116984 hasPublicationYear "2011" @default.
• W2550116984 type Work @default.
• W2550116984 sameAs 2550116984 @default.
• W2550116984 citedByCount "0" @default.
• W2550116984 crossrefType "journal-article" @default.
• W2550116984 hasAuthorship W2550116984A5019566537 @default.
• W2550116984 hasAuthorship W2550116984A5032207811 @default.
• W2550116984 hasAuthorship W2550116984A5042547987 @default.
• W2550116984 hasAuthorship W2550116984A5045981135 @default.
• W2550116984 hasAuthorship W2550116984A5055335263 @default.
• W2550116984 hasAuthorship W2550116984A5060887030 @default.
• W2550116984 hasAuthorship W2550116984A5061164405 @default.
• W2550116984 hasAuthorship W2550116984A5069537100 @default.
• W2550116984 hasAuthorship W2550116984A5080749717 @default.
• W2550116984 hasAuthorship W2550116984A5087192702 @default.
• W2550116984 hasConcept C104317684 @default.
• W2550116984 hasConcept C126322002 @default.
• W2550116984 hasConcept C137061746 @default.
• W2550116984 hasConcept C185592680 @default.
• W2550116984 hasConcept C202751555 @default.
• W2550116984 hasConcept C203014093 @default.
• W2550116984 hasConcept C2779134260 @default.
• W2550116984 hasConcept C2779969927 @default.
• W2550116984 hasConcept C2780674200 @default.
• W2550116984 hasConcept C40767141 @default.
• W2550116984 hasConcept C553184892 @default.
• W2550116984 hasConcept C55493867 @default.
• W2550116984 hasConcept C71924100 @default.
• W2550116984 hasConcept C90924648 @default.
• W2550116984 hasConceptScore W2550116984C104317684 @default.
• W2550116984 hasConceptScore W2550116984C126322002 @default.
• W2550116984 hasConceptScore W2550116984C137061746 @default.
• W2550116984 hasConceptScore W2550116984C185592680 @default.
• W2550116984 hasConceptScore W2550116984C202751555 @default.
• W2550116984 hasConceptScore W2550116984C203014093 @default.
• W2550116984 hasConceptScore W2550116984C2779134260 @default.
• W2550116984 hasConceptScore W2550116984C2779969927 @default.
• W2550116984 hasConceptScore W2550116984C2780674200 @default.
• W2550116984 hasConceptScore W2550116984C40767141 @default.
• W2550116984 hasConceptScore W2550116984C553184892 @default.
• W2550116984 hasConceptScore W2550116984C55493867 @default.
• W2550116984 hasConceptScore W2550116984C71924100 @default.
• W2550116984 hasConceptScore W2550116984C90924648 @default.
• W2550116984 hasLocation W25501169841 @default.
• W2550116984 hasOpenAccess W2550116984 @default.
• W2550116984 hasPrimaryLocation W25501169841 @default.
• W2550116984 hasRelatedWork W2006091929 @default.
• W2550116984 hasRelatedWork W2064324964 @default.
• W2550116984 hasRelatedWork W2118572012 @default.
• W2550116984 hasRelatedWork W2160806857 @default.
• W2550116984 hasRelatedWork W2327216852 @default.
• W2550116984 hasRelatedWork W2333521963 @default.
• W2550116984 hasRelatedWork W2371946969 @default.
• W2550116984 hasRelatedWork W2397018411 @default.
• W2550116984 hasRelatedWork W2407703287 @default.
• W2550116984 hasRelatedWork W2415703012 @default.
• W2550116984 hasRelatedWork W2430978127 @default.
• W2550116984 hasRelatedWork W2467068753 @default.
• W2550116984 hasRelatedWork W2521973269 @default.
• W2550116984 hasRelatedWork W2581168743 @default.
• W2550116984 hasRelatedWork W2609038407 @default.
• W2550116984 hasRelatedWork W2910190479 @default.
• W2550116984 hasRelatedWork W3089593759 @default.
• W2550116984 hasRelatedWork W3109315504 @default.
• W2550116984 hasRelatedWork W3193810866 @default.
• W2550116984 hasRelatedWork W2562341395 @default.
• W2550116984 isParatext "false" @default.
• W2550116984 isRetracted "false" @default.
• W2550116984 magId "2550116984" @default.
• W2550116984 workType "article" @default.