Clinical Operational Tolerance after Kidney Transplantation

Authors

  • G. Roussey-Kesler,

    1. Institut National de la Santé Et de la Recherche Médicale (I.N.S.E.R.M.)- Unité 643: “Immunointervention dans les Allo et xenotransplantations” and Institut de Transplantation Et de Recherche en Transplantation (I.T.E.R.T), CHU-HOTEL DIEU, 30 Bd Jean Monnet, 44035 Nantes Cedex 01, France
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  • M. Giral,

    1. Institut National de la Santé Et de la Recherche Médicale (I.N.S.E.R.M.)- Unité 643: “Immunointervention dans les Allo et xenotransplantations” and Institut de Transplantation Et de Recherche en Transplantation (I.T.E.R.T), CHU-HOTEL DIEU, 30 Bd Jean Monnet, 44035 Nantes Cedex 01, France
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  • A. Moreau,

    1. Service d'Anatomie Pathologie, CHU-HOTEL DIEU, 44 093 Nantes Cedex 01, France
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  • J.-F. Subra,

    1. Service de Néphrologie, CHU, 4 rue Larrey, 49 033 Angers Cedex, France
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  • C. Legendre,

    1. Service de Néphrologie, Hôpital Necker, 149 rue de Sèvres, 75 015 Paris Cedex 15, France
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  • C. Noël,

    1. Service de Néphrologie, Hôpital Calmette, Bd du Professeur Leclerc, 59037 Lille Cedex, France
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  • E. Pillebout,

    1. Service de Néphrologie, Hôpital Saint-Louis, 1 av Claude Vellefaux,75475 Paris, France
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  • S. Brouard,

    1. Institut National de la Santé Et de la Recherche Médicale (I.N.S.E.R.M.)- Unité 643: “Immunointervention dans les Allo et xenotransplantations” and Institut de Transplantation Et de Recherche en Transplantation (I.T.E.R.T), CHU-HOTEL DIEU, 30 Bd Jean Monnet, 44035 Nantes Cedex 01, France
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  • J.-P. Soulillou

    Corresponding author
    1. Institut National de la Santé Et de la Recherche Médicale (I.N.S.E.R.M.)- Unité 643: “Immunointervention dans les Allo et xenotransplantations” and Institut de Transplantation Et de Recherche en Transplantation (I.T.E.R.T), CHU-HOTEL DIEU, 30 Bd Jean Monnet, 44035 Nantes Cedex 01, France
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Abstract

Induction of allograft-specific tolerance and the detection of a “tolerance” state in recipients under immunosuppression with long-term stable graft function are major challenges in transplantation. Clinical “operational tolerance,” defined as stable and acceptable graft function without immunosuppression for years, is a rare event. There is no report on the clinical history of such patients. In this article, we report on the medical history of 10 kidney recipients who display an immunosuppressive drug-free “operational tolerance” for 9.4 ± 5.2 years. Clinical factors that may favor such a tolerant state are underlined. Firstly, most of the patients interrupted immunosuppression over a long time period (until 4 years), which mimics the procedure of intentional immunosuppression weaning following liver transplantation. Secondly, donor age was younger (median 25 years) than the one of the general transplanted population, suggesting that graft quality is one of the conditions favoring “operational tolerance.” Moreover, the “operationally tolerant” recipients may be ‘low responders’ to blood transfusions (PRA 6 ± 5.4%, six blood transfusions). We also show that “operational tolerance” occurs in the presence of anti-donor class II antibodies, as assessed in two patients. Finally, two patients degraded their renal function 9 to 13 years after treatment withdrawal, however only one presented histological lesions of chronic rejection.

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