The Natural History of Clinical Operational Tolerance After Kidney Transplantation Through Twenty-Seven Cases

Authors

  • S. Brouard,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. CIC biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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    • The two first and senior authors contributed equally.

  • A. Pallier,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. CIC biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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    • The two first and senior authors contributed equally.

  • K. Renaudin,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. Service d’anatomie pathologique, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    3. CIC biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    4. Faculté de médecine, Université de Nantes, Nantes, France
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  • Y. Foucher,

    1. Faculté de médecine, Université de Nantes, Nantes, France
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  • R. Danger,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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  • A. Devys,

    1. Laboratoire HLA—Etablissement Français du Sang—Pays de la Loire, Nantes, France
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  • A. Cesbron,

    1. Laboratoire HLA—Etablissement Français du Sang—Pays de la Loire, Nantes, France
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  • C. Guillot-Guegen,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. CIC biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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  • J. Ashton-Chess,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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  • S. Le Roux,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. Faculté de médecine, Université de Nantes, Nantes, France
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  • J. Harb,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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  • G. Roussey,

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
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  • J.-F. Subra,

    1. Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France
    2. Université d'Angers, UMR_S 892, Angers, France
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  • F. Villemain,

    1. Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France
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  • C. Legendre,

    1. Universitè Paris Descartes et Hôpital Necker, Paris, France
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  • F.J. Bemelman,

    1. Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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  • G. Orlando,

    1. Renal Failure and Transplant Unit, San Salvatore Hospital, L'Aquila, Italy, and Department of General Surgery, Section of Transplantation, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  • A. Garnier,

    1. Néphrologie – Médecine Interne – Hypertension Pédiatrique, Hôpital des Enfants, TSA 700034, Toulouse, France
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  • H. Jambon,

    1. Transplantation rénale, CHU Grenoble, Grenoble, France
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  • H. Le Monies De Sagazan,

    1. Service Néphrologie, Hôpital Victor Provo, Roubaix, France
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  • L. Braun,

    1. Hôpital de jour de Néphrologie, service de Néphrologie et Transplantation Rénale, Nouvel hôpital Civil, CHU de Strasbourg, Strasbourg, France
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  • C. Noël,

    1. Nephrology Department, University Hospital of Lille, Lille, France
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  • E. Pillebout,

    1. Nephrology Unit, Hôpital St Louis, Paris, France
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  • M.-C. Moal,

    1. Service de Néphrologie, CHRU de Brest, Brest, France
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  • C. Cantarell,

    1. Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
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  • A. Hoitsma,

    1. Division of Nephrology 464, UMC St Radboud Medical Center, Nijmegen, The Netherlands
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  • M. Ranbant,

    1. Unité de Transplantation Rénale, Hôpital Necker, Paris, France
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  • A. Testa,

    1. E.C.H.O. site du Confluent, Nantes, France
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  • J.-P. Soulillou,

    Corresponding author
    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. Faculté de médecine, Université de Nantes, Nantes, France
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    • The two first and senior authors contributed equally.

  • M. Giral

    1. Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    2. CIC biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France
    3. Faculté de médecine, Université de Nantes, Nantes, France
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    • The two first and senior authors contributed equally.


Jean-Paul Soulillou, jean-paul.soulillou@univ-nantes.fr

Abstract

We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.

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