Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial
2021; Elsevier BV; Volume: 21; Issue: 8 Linguagem: Inglês
10.1111/ajt.16563
ISSN1600-6143
AutoresOriol Bestard, María Meneghini, Elena Crespo, Fréderike J. Bemelman, Martina Koch, Hans‐Dieter Volk, Ondřej Viklický, Magali Giral, Bernhard Banas, Juan Carlos Ruiz, Edoardo Melilli, Hu Liu, Raphaël Duivenvoorden, Björn Nashan, Friedrich Thaiss, Natalie Otto, Gantuja Bold, Maik Stein, Anett Sefrin, Nils Lachmann, Petra Hrubá, Lucia Straňavová, Sophie Brouard, Cécile Braudeau, Gilles Blancho, Miriam Banas, Juan Irure, Sofia Christakoudi, Alberto Sánchez‐Fueyo, Kathryn J. Wood, Petra Reinke, Josep M. Grinyó,
Tópico(s)Neurological Complications and Syndromes
ResumoAmerican Journal of TransplantationVolume 21, Issue 8 p. 2833-2845 ORIGINAL ARTICLE Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial Oriol Bestard, Corresponding Author obestard@bellvitgehospital.cat orcid.org/0000-0001-9468-7920 Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain Correspondence Oriol Bestard, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain. Email: obestard@bellvitgehospital.cat Petra Reinke, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany. Email: Petra.reinke@charite.deSearch for more papers by this authorMaria Meneghini, orcid.org/0000-0001-7307-923X Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorElena Crespo, Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorFrederike Bemelman, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorMartina Koch, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorHans D. Volk, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorOndrej Viklicky, orcid.org/0000-0003-1049-2195 Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorMagali Giral, orcid.org/0000-0001-7641-1592 Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorBernhard Banas, Department of Nephrology, University Medical Center Regensburg, Regensburg, GermanySearch for more papers by this authorJuan C. Ruiz, Department of Nephrology, Hospital Universitario "Marqués de Valdecilla", Instituto de Investigación "Marqués de Valdecilla" (IDIVAL, Santander, SpainSearch for more papers by this authorEdoardo Melilli, orcid.org/0000-0001-6965-3745 Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorLiu Hu, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorRaphael van Duivenvoorden, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorBjörn Nashan, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorFriedrich Thaiss, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorNatalie M. Otto, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorGantuja Bold, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorMaik Stein, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorAnett Sefrin, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorNils Lachmann, HLA-Laboratory, Charité-Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorPetra Hruba, Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorLucia Stranavova, Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorSophie Brouard, orcid.org/0000-0002-6398-1315 Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorCécile Braudeau, Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France CHU Nantes, Laboratoire d'immunologie, CIMNA, Nantes, FranceSearch for more papers by this authorGilles Blancho, Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorMiriam Banas, Department of Nephrology, University Medical Center Regensburg, Regensburg, GermanySearch for more papers by this authorJuan Irure, Immunology Department, University Hospital Marqués de Valdecilla-IDIVAL, Santander, SpainSearch for more papers by this authorSophia Christakoudi, Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UKSearch for more papers by this authorAlberto Sanchez-Fueyo, orcid.org/0000-0002-8316-3504 Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UKSearch for more papers by this authorKathryn J. Wood, Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UKSearch for more papers by this authorPetra Reinke, Corresponding Author Petra.reinke@charite.de BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany Correspondence Oriol Bestard, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain. Email: obestard@bellvitgehospital.cat Petra Reinke, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany. Email: Petra.reinke@charite.deSearch for more papers by this authorJosep M. Grinyó, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this author Oriol Bestard, Corresponding Author obestard@bellvitgehospital.cat orcid.org/0000-0001-9468-7920 Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain Correspondence Oriol Bestard, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain. Email: obestard@bellvitgehospital.cat Petra Reinke, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany. Email: Petra.reinke@charite.deSearch for more papers by this authorMaria Meneghini, orcid.org/0000-0001-7307-923X Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorElena Crespo, Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorFrederike Bemelman, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorMartina Koch, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorHans D. Volk, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorOndrej Viklicky, orcid.org/0000-0003-1049-2195 Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorMagali Giral, orcid.org/0000-0001-7641-1592 Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorBernhard Banas, Department of Nephrology, University Medical Center Regensburg, Regensburg, GermanySearch for more papers by this authorJuan C. Ruiz, Department of Nephrology, Hospital Universitario "Marqués de Valdecilla", Instituto de Investigación "Marqués de Valdecilla" (IDIVAL, Santander, SpainSearch for more papers by this authorEdoardo Melilli, orcid.org/0000-0001-6965-3745 Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this authorLiu Hu, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorRaphael van Duivenvoorden, Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the NetherlandsSearch for more papers by this authorBjörn Nashan, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorFriedrich Thaiss, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySearch for more papers by this authorNatalie M. Otto, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorGantuja Bold, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorMaik Stein, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorAnett Sefrin, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, GermanySearch for more papers by this authorNils Lachmann, HLA-Laboratory, Charité-Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorPetra Hruba, Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorLucia Stranavova, Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech RepublicSearch for more papers by this authorSophie Brouard, orcid.org/0000-0002-6398-1315 Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorCécile Braudeau, Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France CHU Nantes, Laboratoire d'immunologie, CIMNA, Nantes, FranceSearch for more papers by this authorGilles Blancho, Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, FranceSearch for more papers by this authorMiriam Banas, Department of Nephrology, University Medical Center Regensburg, Regensburg, GermanySearch for more papers by this authorJuan Irure, Immunology Department, University Hospital Marqués de Valdecilla-IDIVAL, Santander, SpainSearch for more papers by this authorSophia Christakoudi, Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UKSearch for more papers by this authorAlberto Sanchez-Fueyo, orcid.org/0000-0002-8316-3504 Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UKSearch for more papers by this authorKathryn J. Wood, Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UKSearch for more papers by this authorPetra Reinke, Corresponding Author Petra.reinke@charite.de BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany Correspondence Oriol Bestard, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain. Email: obestard@bellvitgehospital.cat Petra Reinke, BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany. Email: Petra.reinke@charite.deSearch for more papers by this authorJosep M. Grinyó, Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, SpainSearch for more papers by this author First published: 16 March 2021 https://doi.org/10.1111/ajt.16563 Maria Meneghini and Elena Crespo are co-second authors. Petra Reinke and Josep M Grinyó are co-senior authors. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E−) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E− (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E− patients, notably E−/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E−/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation. Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding authors upon reasonable request. Supporting Information Filename Description ajt16563-sup-0001-Supinfo.pdfPDF document, 471.7 KB Supplementary Material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume21, Issue8August 2021Pages 2833-2845 AST and ASTS members - please log in via your Society website for full journal access.AST Members >> ASTS Members >> RelatedInformation
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