Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial.

Autor: Bestard O; Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain.; Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain., Meneghini M; Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain.; Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain., Crespo E; Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain., Bemelman F; Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands., Koch M; Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Volk HD; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Viklicky O; Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.; Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Giral M; Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France., Banas B; Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany., Ruiz JC; Department of Nephrology, Hospital Universitario 'Marqués de Valdecilla', Instituto de Investigación 'Marqués de Valdecilla' (IDIVAL, Santander, Spain., Melilli E; Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain., Hu L; Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands., van Duivenvoorden R; Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands., Nashan B; Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Thaiss F; Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Otto NM; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Bold G; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Stein M; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Sefrin A; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Lachmann N; HLA-Laboratory, Charité-Universitätsmedizin Berlin, Berlin, Germany., Hruba P; Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.; Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Stranavova L; Transplant Laboratory, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.; Department of Nephrology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Brouard S; Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France., Braudeau C; Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France.; CHU Nantes, Laboratoire d'immunologie, CIMNA, Nantes, France., Blancho G; Nantes Université, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France., Banas M; Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany., Irure J; Immunology Department, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain., Christakoudi S; Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UK., Sanchez-Fueyo A; Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Sciences & Medicine, King's College London, London, UK., Wood KJ; Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Reinke P; BeCAT, BCRT, and Department of Nephrology & Intensive Care, Charité Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany., Grinyó JM; Kidney Transplant Unit, Nephrology department, Bellvitge University Hospital, IDIBELL, Barcelona University, Barcelona, Spain.; Nephrology and Transplantation Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Aug; Vol. 21 (8), pp. 2833-2845. Date of Electronic Publication: 2021 Apr 15.
DOI: 10.1111/ajt.16563
Abstrakt: 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.
(© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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