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dc.contributor.authorLangton, David J
dc.contributor.authorBhalekar, Rohan M
dc.contributor.authorJoyce, Thomas J
dc.contributor.authorRushton, Stephen P
dc.contributor.authorWainwright, Benjamin J
dc.contributor.authorNargol, Matthew E
dc.contributor.authorShyam, Nish
dc.contributor.authorLie, Benedicte
dc.contributor.authorPabbruwe, Moreica
dc.contributor.authorStewart, Alan J.
dc.contributor.authorWaller, Susan
dc.contributor.authorNatu, Shonali
dc.contributor.authorRen, Renee
dc.contributor.authorHornick, Rachelle
dc.contributor.authorDarlay, Rebecca
dc.contributor.authorSu, Edwin P
dc.contributor.authorNargol, Antoni V F
dc.identifier.citationLangton , D J , Bhalekar , R M , Joyce , T J , Rushton , S P , Wainwright , B J , Nargol , M E , Shyam , N , Lie , B , Pabbruwe , M , Stewart , A J , Waller , S , Natu , S , Ren , R , Hornick , R , Darlay , R , Su , E P & Nargol , A V F 2022 , ' The influence of HLA genotype on the development of metal hypersensitivity following joint replacement ' , Communications Medicine , vol. 2 , 73 .
dc.identifier.otherPURE: 279986202
dc.identifier.otherPURE UUID: 870bd032-4856-47e0-824e-d52740365409
dc.identifier.otherORCID: /0000-0003-4580-1840/work/115309389
dc.descriptionWe thank Innovate UK Edge for providing funding to allow this research to be carried out.en
dc.description.abstractBackground  Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype44 and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time dependent receiver operator curves. Results Using next generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1%53 for pre-operative and post-operative models respectively. Conclusions The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient specific responses to different biomaterials.
dc.relation.ispartofCommunications Medicineen
dc.rightsCopyright © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.subjectQH426 Geneticsen
dc.subjectRD Surgeryen
dc.titleThe influence of HLA genotype on the development of metal hypersensitivity following joint replacementen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.description.statusPeer revieweden

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