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The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation.
Ceulemans, L J; Braza, F; Monbaliu, D; Jochmans, I; De Hertogh, G; Du Plessis, J; Emonds, M-P; Kitade, H; Kawai, M; Li, Y; Zhao, X; Koshiba, T; Sprangers, B; Brouard, S; Waer, M; Pirenne, J.
Afiliación
  • Ceulemans LJ; Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Braza F; Institut de Recherche en Transplantation, Urologie et Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, University of Nantes, Nantes, France.
  • Monbaliu D; Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Jochmans I; Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • De Hertogh G; Translational Cell and Tissue Research, University Hospitals Leuven, and Department of Imaging and Pathology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Du Plessis J; Division of Hepatology, University Hospitals Leuven, and Department of Clinical and Experimental Medicine, University of Leuven, KU Leuven, Leuven, Belgium.
  • Emonds MP; Laboratory for Histocompatibility and Immunogenetics (HILA), Red Cross Flanders, Mechelen, Belgium.
  • Kitade H; Experimental Transplantation, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Kawai M; Experimental Transplantation, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Li Y; Experimental Transplantation, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Zhao X; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Koshiba T; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Sprangers B; Experimental Transplantation, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Brouard S; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Waer M; Experimental Transplantation, University Hospitals Leuven, and Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
  • Pirenne J; Institut de Recherche en Transplantation, Urologie et Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, University of Nantes, Nantes, France.
Am J Transplant ; 16(10): 2973-2985, 2016 10.
Article en En | MEDLINE | ID: mdl-27037650
Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA- Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Rechazo de Injerto / Supervivencia de Injerto / Tolerancia Inmunológica / Enfermedades Intestinales / Intestinos Tipo de estudio: Etiology_studies / Guideline / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Rechazo de Injerto / Supervivencia de Injerto / Tolerancia Inmunológica / Enfermedades Intestinales / Intestinos Tipo de estudio: Etiology_studies / Guideline / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos