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dc.contributor.authorWiebe, Chris
dc.contributor.authorKosmoliaptsis, Vasilis
dc.contributor.authorPochinco, Denish
dc.contributor.authorTaylor, Craig J
dc.contributor.authorNickerson, Peter
dc.date.accessioned2018-04-19T09:45:33Z
dc.date.available2018-04-19T09:45:33Z
dc.date.issued2018-08
dc.identifier.issn0041-1337
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275000
dc.description.abstractBACKGROUND: Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level; however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression. METHODS: HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development. The molecular mismatch scores were evaluated in multivariate models of posttransplant dnDSA-free survival. RESULTS: Eplet mismatch correlated with amino acid mismatch and electrostatic mismatch (R = 0.85-0.96). HLA-DR dnDSA-free survival correlated with HLA-DR eplet mismatch (hazards ratio [HR], 2.50 per 10 eplets mismatched; P < 0.0001), amino acid mismatch (HR, 1.49 per 10 amino acids mismatched; P < 0.0001), and electrostatic mismatch (HR, 1.23 per 10 units mismatched; P < 0.0001). HLA-DQ dnDSA-free survival correlated with HLA-DQ eplet mismatch (HR, 1.98 per 10 eplets mismatched; P < 0.0001), amino acid mismatch (HR, 1.24 per 10 amino acids mismatched; P < 0.0001), and electrostatic mismatch (HR, 1.14 per 10 units mismatched; P < 0.0001). All 3 methods were significant multivariate correlates of dnDSA development after adjustment for recipient age, baseline immunosuppression, and nonadherence. CONCLUSIONS: HLA molecular mismatch represents a precise method of alloimmune risk assessment for renal transplant patients. The method used to determine the molecular mismatch is likely to be driven by familiarity and ease of use as highly correlated results are produced by each method.
dc.format.mediumPrint
dc.languageeng
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectKidney Failure, Chronic
dc.subjectAntibodies
dc.subjectHLA Antigens
dc.subjectHistocompatibility Testing
dc.subjectDisease-Free Survival
dc.subjectImmunosuppression
dc.subjectKidney Transplantation
dc.subjectMultivariate Analysis
dc.subjectProportional Hazards Models
dc.subjectRisk Assessment
dc.subjectFollow-Up Studies
dc.subjectGraft Survival
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectStatic Electricity
dc.subjectYoung Adult
dc.titleA Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity.
dc.typeArticle
prism.endingPage1343
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameTransplantation
prism.startingPage1338
prism.volume102
dc.identifier.doi10.17863/CAM.22156
dcterms.dateAccepted2018-01-09
rioxxterms.versionofrecord10.1097/TP.0000000000002117
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidKosmoliaptsis, Vasilis [0000-0001-7298-1387]
dc.identifier.eissn1534-6080
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEvelyn Trust (14/25)
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idAddenbrooke's Charitable Trust (ACT) (CT/03/16 B (vii))
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR-PDF-2016-09-065)
cam.issuedOnline2018-07-25
cam.orpheus.successThu Jan 30 12:59:36 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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