Lydia M. Kwast
Utrecht University
CytotoxicityInnate immune systemAntigenKineticsImmunotoxicologySerum albuminCD8Affinity chromatographyChemistryPre-clinical developmentAcquired immune systemConjugateIn vitroImmunologyIn vivoEx vivoAlbuminSensitizationOral administrationAdjuvantGranulocyteHuman serum albuminAcetaminophenMesenteric lymph nodesImmunityDiversity (business)DiclofenacDrugSurpriseLymph nodeSpleenNAPQIStable Isotope LabelingImmunopotentiatorToxicityLife spanCellular lifeCell separationBlood neutrophilsChromatographyEffectorBiochemistryHomeostasisComputational biologyMedicineGerontologyBiologyImmune systemDrug metabolismPharmacology
10Publications
5H-index
578Citations
Publications 10
Newest
#1Lydia M. Kwast (UU: Utrecht University)H-Index: 5
#2Tetsuo Aida (Daiichi Sankyo)H-Index: 6
Last. Raymond Pieters (UU: Utrecht University)H-Index: 36
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Immune-mediated drug hypersensitivity reactions (IDHR) may result from immuno-sensitization to a drug-induced neo-antigen. They rarely occur in patients and are usually not predicted preclinically using standard toxicity studies. To assess the potential of a drug to induce T-cell sensitization, trinitrophenyl (TNP)-Ficoll was used here as a bystander antigen in animal experiments. TNP-Ficoll will only elicit TNP-specific IgG antibodies in the presence of non-cognate T-cell help. Therefore, the p...
1 CitationsSource
#1Lydia M. Kwast (UU: Utrecht University)H-Index: 5
#2Daniëlle Fiechter (UU: Utrecht University)H-Index: 8
Last. Raymond Pieters (UU: Utrecht University)H-Index: 36
view all 8 authors...
The development of immune-dependent drug hypersensitivity reactions (IDHR) is likely to involve activation of the innate immune system to stimulate neo-antigen specific T-cells. Previously it has been shown that, upon oral exposure to several drugs with immune-adjuvant capacity, mice developed T-cell-dependent responses to TNP-OVA. These results were indicative of the adjuvant potential of these drugs. The present study set out to evaluate the nature of this adjuvant potential by focusing on ear...
2 CitationsSource
#1Liset Westera (UU: Utrecht University)H-Index: 8
#2Julia Drylewicz (UU: Utrecht University)H-Index: 17
Last. José A. M. Borghans (UU: Utrecht University)H-Index: 31
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Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art technique for in vivo quantification of cellular life spans. Yet, even leukocyte life span estimates on the basis of stable isotope labeling can vary up to 10-fold among laboratories. We investigated whether these differences could be the result of v...
78 CitationsSource
#1Linda Switzar (VU: VU University Amsterdam)H-Index: 7
#2Lydia M. Kwast (UU: Utrecht University)H-Index: 5
Last. Wilfried M. A. Niessen (VU: VU University Amsterdam)H-Index: 56
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The formation of drug-protein adducts following the bioactivation of drugs to reactive metabolites has been linked to adverse drug reactions (ADRs) and is a major complication in drug discovery and development. Identification and quantification of drug-protein adducts in vivo may lead to a better understanding of drug toxicity, but is challenging due to their low abundance in the complex biological samples. Human serum albumin (HSA) is a well-known target of reactive drug metabolites due to the ...
12 CitationsSource
#1Janesh Pillay (UU: Utrecht University)H-Index: 20
#2Ineke den Braber (UU: Utrecht University)H-Index: 8
Last. Leo Koenderman (UU: Utrecht University)H-Index: 80
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We have read the comments raised by Tofts and colleagues and Li and colleagues with great interest. We share their surprise about our finding that—under normal homeostatic conditions—peripheral blood neutrophils have an average life span of 5.4 days, and we welcome their constructive replies to
14 CitationsSource
#1Lydia M. Kwast (UU: Utrecht University)H-Index: 5
#2Daniëlle Fiechter (UU: Utrecht University)H-Index: 8
Last. Raymond Pieters (UU: Utrecht University)H-Index: 36
view all 7 authors...
Immune-mediated drug hypersensitivity reactions are important causes of black box warnings and drug withdrawals. Despite the high demand for preclinical screening tools, no validated in vitro or in vivo models are available. In the current study, we used a previously described oral administration model using trinitrophenyl-ovalbumin (TNP-OVA) as an antigen to report immuno-adjuvating effects of the analgesic drug acetaminophen (APAP) and its nonhepatotoxic regioisomer 3#-hydroxyacetanilide (AMAP...
8 CitationsSource
#1Janesh PillayH-Index: 20
#2Ineke den Braber (UU: Utrecht University)H-Index: 8
Last. Leo KoendermanH-Index: 80
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Neutrophils are essential effector cells of the innate immune response and are indispensable for host defense. Apart from their antimicrobial functions, neutrophils inform and shape subsequent immunity. This immune modulatory functionality might however be considered limited because of their generally accepted short lifespan (< 1 day). In contrast to the previously reported short lifespans acquired by ex vivo labeling or manipulation, we show that in vivo labeling in humans with the use of 2H2O ...
485 CitationsSource
#1Irene S. Ludwig (UU: Utrecht University)H-Index: 12
#2Lydia M. Kwast (UU: Utrecht University)H-Index: 5
Last. Raymond Pieters (UU: Utrecht University)H-Index: 36
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: New chemical entities are tested in general toxicity assays during development before entering clinical trials. However, immunosensitization of these entities is not tested on a standard basis. There are no in vitro or in vivo standardized methods available for testing immunosensitization or immunostimulation. In this chapter, we describe a tiered strategy oral exposure model for assessing immunosensitization or immunostimulation capacity of low molecular weight compounds. The strategy starts ...
1 CitationsSource
Last. Dejan MilutinovicH-Index: 15
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Last. Dejan MilutinovicH-Index: 15
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