Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection

Article Article scientifique Article Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection eng 2018 author Chen Chien-Chia author Pouliquen Eric author Broisat Alexis author Andreata Francesco author Racapé Maud author Bruneval Patrick author Kessler Laurence author Ahmadi Mitra author Bacot Sandrine author Saison-Delaplace Carole author Marcaud Marina author Van Huyen Jean-Paul Duong author Loupy Alexandre author Villard Jean 29595 author Demuylder-Mischler Sandrine author Berney Thierry 63319 author Morelon Emmanuel author Tsai Meng-Kun author Kolopp-Sarda Marie-Nathalie author Koenig Alice author Mathias Virginie author Ducreux Stéphanie author Ghezzi Catherine author Dubois Valérie Marie-José 90192 author Nicoletti Antonino author Defrance Thierry author Thaunat Olivier 219-232 10.1172/JCI93542 29202467 0021-9738 Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies. Dewey 616 Dewey 617 56 Département de médecine 221 57 Département de chirurgie 222 false 357 La transplantation d'îlots de Langerhans 623 298 Transplantation immunologie et osteoimmunologie 561 Journal of Clinical Investigation 128 1 f43a2d55-b56d-4dfc-945d-073d1de507b0 Article (Published version) Public jci-128-93542.pdf 13596137 application/pdf OA OTHER openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection	Journal of Clinical Investigation			2018	475	279

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Dubois, Valérie Marie-José