https://scholars.lib.ntu.edu.tw/handle/123456789/434600
標題: | Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection | 作者: | CHIEN-CHIA CHEN Pouliquen E. Broisat A. Andreata F. Racap? M. Bruneval P. Kessler L. Ahmadi M. Bacot S. Saison-Delaplace C. Marcaud M. Van Huyen J.-P.D. Loupy A. Villard J. Demuylder-Mischler S. Berney T. Morelon E. MENG-KUN TSAI Kolopp-Sarda M.-N. Koenig A. Mathias V. Ducreux S. Ghezzi C. Dubois V. Nicoletti A. Defrance T. Thaunat O. |
公開日期: | 2018 | 出版社: | American Society for Clinical Investigation | 卷: | 128 | 期: | 1 | 起(迄)頁: | 219-232 | 來源出版物: | Journal of Clinical Investigation | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040172984&doi=10.1172%2fJCI93542&partnerID=40&md5=d9e95e1938a0988b376bf15c8328de3d https://scholars.lib.ntu.edu.tw/handle/123456789/434600 |
ISSN: | 0021-9738 | DOI: | 10.1172/JCI93542 | SDG/關鍵字: | alternative complement pathway C3 C5 convertase; antiserum; classical complement pathway C3 C5 convertase; complement; complement component C1q; complement component C3; complement component C3a; complement component C3b; complement membrane attack complex; HLA antibody; immunoglobulin; immunoglobulin G; immunoglobulin G2a; alloantibody; allogeneic stem cell transplantation; allograft; animal cell; animal experiment; animal model; animal tissue; antibody mediated rejection; Article; capillary flow; chimera; clinical article; controlled study; endothelium cell; graft recipient; graft survival; heart transplantation; human; humoral immunity; in vitro study; in vivo study; interstitium; mouse; nonhuman; pancreas islet; pancreas islet cell; priority journal; retrospective study; streptozotocin-induced diabetes mellitus; vascular lesion; vascularization; allograft; animal; female; graft rejection; histocompatibility; male; metabolism; pancreas islet transplantation; pathology; vascular endothelium; Allografts; Animals; Endothelium, Vascular; Female; Graft Rejection; Graft Survival; Humans; Islets of Langerhans Transplantation; Isoantibodies; Male; Mice; Transplantation Chimera |
顯示於: | 醫學系 |
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