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Amsterdam-Zuidoost, Netherlands

Thijs C.,Maastricht University | Muller A.,University of Hamburg | Rist L.,Paracelsus Hospital Richterswil | Kummeling I.,Maastricht University | And 7 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: One of the explanations for the increasing prevalence of atopic diseases is a relative low perinatal supply of n-3 fatty acids. However, this does not explain the protective effects of whole-fat dairy products or high levels of transfatty acids in breast milk, observed in some studies. We evaluated the role of perinatal supply of fatty acids in the early development of atopic eczema and allergic sensitisation. Methods: Fatty acids, including n-3 long-chain polyunsaturated fatty acids (LCPs) as well as ruminant fatty acids (rumenic acid, cis-9,trans-11-C18:2 conjugated linoleic acid; and vaccenic acid, trans-11-C18:1), were determined in breast milk sampled at 1 month postpartum from 310 mother-infant pairs in the KOALA Birth Cohort Study, the Netherlands. Children were followed for atopic outcomes until 2 years of age. Results: Higher concentrations of n-3 LCPs as well as ruminant fatty acids were associated with lower risk of (1) parent-reported eczema, (2) atopic dermatitis (UK Working Party criteria), and (3) sensitisation at age 1 year (as revealed by specific serum IgE levels to cow's milk, hen's egg and/or peanut). In multivariable logistic regression analysis, the inverse associations between ruminant fatty acid concentrations in breast milk and atopic outcomes were found to be independent from n-3 LCPs. Conclusions: The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations. © 2010 John Wiley & Sons A/S. Source


de Haas M.,Sanquin | Finning K.,National Health Service Blood and Transplant | Massey E.,National Health Service Blood and Transplant | Roberts D.J.,National Health Service Blood and Transplant | Roberts D.J.,University of Oxford
Transfusion Medicine | Year: 2014

The new British Committee for Standards in Haematology (BCSH) guidelines for the use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the use of anti-D in ectopic pregnancy and after red cell salvage during caesarean section, of dosing with different preparations and distinguishing non-immune and immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus (Rh) D alloimmunisation during the third trimester is well established and requires careful and well-audited local implementation to achieve the maximum public health benefit. In the UK, such scrutiny may be provided by the reporting of failed anti-D prophylaxis at women who have produced an immune anti-D that is detectable for the first time in the current pregnancy through the voluntary Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD genotyping would avoid giving anti-D to RhD negative women carrying an RhD negative fetus. RAADP is directed by fetal RHD genotyping in some countries in Northern Europe led by the Netherlands and Denmark. The economic case for RAADP directed by fetal RHD genotyping needs to be carefully evaluated and in England is under consideration by National Institute for Health and Clinical Excellence (NICE). Possible future developments include the use of monoclonal anti-D preparations, now in advanced clinical trials, and also testing the hypothesis that directed RAADP from early in the second trimester may further reduce anti-D immunisation. © 2014 The Authors. Transfusion Medicine © 2014 British Blood Transfusion Society. Source


Tran L.,Netherlands Cancer Institute | Baars J.W.,Netherlands Cancer Institute | Aarden L.,Sanquin | Beijnen J.H.,Netherlands Cancer Institute | And 2 more authors.
Human Antibodies | Year: 2010

Background: In this study, we investigated the pharmacokinetics of rituximab in patients with CD20 positive non-Hodgkin lymphoma, to get more insight into the factors that influence the pharmacokinetics of rituximab. This may aid to understand variability of treatment outcome, in patients with a CD20 positive malignancy treated with rituximab. Methods: In this study, patients with a CD20 positive B-cell malignancy who were treated with rituximab containing regimens were included. Induction treatment schedules consisted of a combination of rituximab with chemotherapy for 4-8 cycles. Maintenance treatment consisted of a 2 or 3-monthly dose of 375 mg/m^{2} rituximab intravenously for 2 years. On the day of the treatment with rituximab, preinfusion blood samples were taken. Also, after the end of treatment, selected blood samples were taken. Rituximab levels were measured with a validated enzyme-linked immunosorbent assay (ELISA). An antigen binding assay was applied for determination of human-antibodies against chimeric-antibodies (HACAs). Results: Eight patients were on induction therapy. Rituximab levels of one patient on induction therapy remained very low after the first course. This patient had a chronic lymphoid leukemia with circulating tumor cells and a high tumor burden. Apart from one patient with mantle cell lymphoma, all patients on induction therapy had a complete response. Five patients were on maintenance therapy. Trough levels of 4 patients on three-monthly schedule maintenance therapy remained constant, with a median concentration of 6 μ g/mL (range 0.5-11.7 μg/mL). One patient had a relapse during his maintenance treatment. The elimination half-life at steady state of rituximab in all patients was estimated to be 19.2 (± 15.2%) days with a between-subject variability of 54%, indicating wide variability. Possible pharmacokinetic-pharmacodynamic relationship was observed as rituximab levels of the non-responders remained low compared to the rituximab levels of the responders. For all patients, concentration of HACAs remained below the quantification limit. Summary/conclusion: Considerable inter-individual variability of rituximab levels was observed. Although the patient population was small, the results support the need for more research into the pharmacokinetics and factors that might influence the pharmacokinetic- pharmacodynamic relationships of rituximab in patients with non-Hodgkin lymphoma. © 2010 IOS Press and the authors. All rights reserved. Source


Guhr T.,University of Amsterdam | Bloem J.,Sanquin | Derksen N.I.L.,University of Amsterdam | Wuhrer M.,Leiden University | And 3 more authors.
PLoS ONE | Year: 2011

Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA (+)) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA (+) using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA (+) 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA (+) had no effect on the platelet count. Serum levels of IVIg and IVIg-SA (+) were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model. © 2011 Guhr et al. Source


Denys B.,Erasmus Medical Center | Denys B.,Ghent University | Van Der Sluijs-Gelling A.J.,Dutch Childhood Oncology Group | Homburg C.,Sanquin | And 6 more authors.
Leukemia | Year: 2013

Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are obtained in 5-20% of samples. We evaluated whether 6-color FCM, including additional markers and new marker combinations, improved the results. Bone marrow samples were obtained from 363 ALL patients at day 15, 33 and 78 and MRD was analyzed using 6-color (218 patients) or 4-color (145 patients) FCM in parallel to routine PCR-based MRD diagnostics. Compared with 4-color FCM, 6-color FCM significantly improved the concordance with PCR-based MRD data (88% versus 96%); particularly the specificity of the MRD analysis improved. However, PCR remained more sensitive at levels <0.01%. MRD-based risk groups were similar between 6-color FCM and PCR in 68% of patients, most discrepancies being medium risk by PCR and standard risk by FCM. Alternative interpretation of the PCR data, aimed at prevention of false-positive MRD results, changed the risk group to standard risk in half (52%) of these discordant cases. In conclusion, 6-color FCM significantly improves MRD analysis in ALL but remains less sensitive than PCR-based MRD-diagnostics. © 2013 Macmillan Publishers Limited All rights reserved. Source

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