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dc.contributor.authorWeng, Ying-Jan
dc.contributor.authorHusebekk, Anne
dc.contributor.authorSkogen, Bjørn Ragnar
dc.contributor.authorKillie, Mette Kjær
dc.contributor.authorLin, Liang-Tzung
dc.contributor.authorBurnouf, Thierry
dc.date.accessioned2017-01-30T14:24:24Z
dc.date.available2017-01-30T14:24:24Z
dc.date.issued2016-09-14
dc.description.abstractFetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements opening perspectives for the prevention of FNAIT.en_US
dc.descriptionCopyright: © 2016 Weng et al. This is an open access article distributed under the terms of the <a href="https://creativecommons.org/licenses/by/4.0/"> Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br> DOI: <a href="http://www.dx.doi.org/10.1371/journal.pone.0162973">10.1371/journal.pone.0162973</a>en_US
dc.identifier.citationWeng, Husebekk A, Skogen br, Killie MK, Lin L, Burnouf T. Anti-human platelet antigen-1α immunoglobulin G preparation intended to prevent fetal and neonatal alloimmune thrombocytopenia. PLoS ONE. 2016;11(9)en_US
dc.identifier.cristinIDFRIDAID 1402046
dc.identifier.doi10.1371/journal.pone.0162973
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/10233
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS ONE
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical immunology: 716en_US
dc.titleAnti-human platelet antigen-1α immunoglobulin G preparation intended to prevent fetal and neonatal alloimmune thrombocytopeniaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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