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dc.contributor.authorMallon, Dermot Hen
dc.contributor.authorKling, Christianeen
dc.contributor.authorRobb, Matthewen
dc.contributor.authorEllinghaus, Evaen
dc.contributor.authorBradley, J Andrewen
dc.contributor.authorTaylor, Craig Jen
dc.contributor.authorKabelitz, Dieteren
dc.contributor.authorKosmoliaptsis, Vasilisen
dc.date.accessioned2018-12-06T00:30:18Z
dc.date.available2018-12-06T00:30:18Z
dc.date.issued2018-12en
dc.identifier.issn0022-1767
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286345
dc.description.abstractIn transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesised that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared to recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level (electrostatic mismatch score-three dimensional; EMS-3D). We then examined humoral alloimmune responses in healthy females subjected to a standardised injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
dc.description.sponsorshipNIHR
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherAmerican Association of Immunologists
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumansen
dc.subjectIsoantibodiesen
dc.subjectHLA-DQ Antigensen
dc.subjectIsoantigensen
dc.subjectHistocompatibility Testingen
dc.subjectKidney Transplantationen
dc.subjectHistocompatibilityen
dc.subjectGraft Rejectionen
dc.subjectTissue Donorsen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectStatic Electricityen
dc.subjectImmunity, Humoralen
dc.subjectHLA-DRB1 Chainsen
dc.subjectTransplant Recipientsen
dc.titlePredicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential.en
dc.typeArticle
prism.endingPage3792
prism.issueIdentifier12en
prism.publicationDate2018en
prism.publicationNameJournal of immunology (Baltimore, Md. : 1950)en
prism.startingPage3780
prism.volume201en
dc.identifier.doi10.17863/CAM.33656
dcterms.dateAccepted2018-10-02en
rioxxterms.versionofrecord10.4049/jimmunol.1800683en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12en
dc.contributor.orcidMallon, Dermot H [0000-0001-7434-1201]
dc.contributor.orcidKling, Christiane [0000-0002-8809-9708]
dc.contributor.orcidEllinghaus, Eva [0000-0003-2914-3382]
dc.contributor.orcidKosmoliaptsis, Vasileios [0000-0001-7298-1387]
dc.identifier.eissn1550-6606
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEvelyn Trust (14/25)
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idRoyal College of Surgeons of England (Martin Coomer 10/07/2014)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR-PDF-2016-09-065)


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