T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
Frontiers in Immunology, vol. 12, pp. 784040
Abstract
CD4+T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.
Authors 44
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Emma T. M. Peereboom corresponding
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Aichi Medical University · Japanese Red Cross Nagoya Daini Hospital
Affiliation as printed
Department of Kidney Diseases and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
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Affiliation as printed
PIRCHE AG, Berlin, Germany
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Department of Nephrology, Amsterdam University Medical Center, Amsterdam, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Department of Nephrology, Amsterdam University Medical Center, Amsterdam, Netherlands
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Affiliation as printed
Department of Immunogenetics/HLA Diagnostic, Sanquin Diagnostic Services, Amsterdam, Netherlands
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Affiliation as printed
Department of Immunogenetics/HLA Diagnostic, Sanquin Diagnostic Services, Amsterdam, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
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Amsterdam University Medical Centers
Affiliation as printed
Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
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Affiliation as printed
Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
Department of Nephrology, Erasmus MC, Rotterdam, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Affiliation as printed
Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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