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dc.contributor.authorKumpel, Belinda M.
dc.contributor.authorSaldova, Radka
dc.contributor.authorKoeleman, Carolien A. M.
dc.contributor.authorAbrahams, Jodie L.
dc.contributor.authorEderveen, Agnes Hipgrave
dc.contributor.authorArmour, Kathryn L.
dc.contributor.authorOlovnikova, Natalia I.
dc.contributor.authorVidarsson, Gestur
dc.contributor.authorKapur, Rick
dc.contributor.authorRudd, Pauline M.
dc.contributor.authorWuhrer, Manfred
dc.date.accessioned2021-01-29T17:22:30Z
dc.date.available2021-01-29T17:22:30Z
dc.date.issued2020-01-30
dc.date.submitted2019-01-03
dc.identifier.others41598-019-57393-9
dc.identifier.other57393
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316867
dc.description.abstractAbstract: Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in FcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADCC activity. In vivo, two B mAb-Ds with 77–81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57–83% but 15–58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/45/221
dc.subject/631/61/475
dc.subject/631/250/251/1574
dc.subject/692/699/1541
dc.subject/692/308/153
dc.subject/13/1
dc.subject/13/106
dc.subject/13/62
dc.subject/82/58
dc.subject/101/47
dc.subjectarticle
dc.titleAnti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy
dc.typeArticle
dc.date.updated2021-01-29T17:22:29Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume10
dc.identifier.doi10.17863/CAM.63980
dcterms.dateAccepted2019-12-17
rioxxterms.versionofrecord10.1038/s41598-019-57393-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidEderveen, Agnes Hipgrave [0000-0003-1689-0442]
dc.contributor.orcidVidarsson, Gestur [0000-0001-5621-003X]
dc.contributor.orcidKapur, Rick [0000-0002-1608-876X]
dc.contributor.orcidWuhrer, Manfred [0000-0002-0814-4995]
dc.identifier.eissn2045-2322


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)