{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:41:55Z","timestamp":1791859315954,"version":"4.3.4"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ab-mediated rejection (AMR) remains the primary obstacle in presensitized patients following organ transplantation, as it is refractory to anti-T cell therapy and can lead to early graft loss. Complement plays an important role in the process of AMR. In the present study, a murine model was designed to mimic AMR in presensitized patients. This model was used to evaluate the effect of blocking the fifth complement component (C5) with an anti-C5 mAb on prevention of graft rejection. BALB\/c recipients were presensitized with C3H donor skin grafts 7 days before heart transplantation from the same donor strain. Heart grafts, transplanted when circulating anti-donor IgG Abs were at peak levels, were rejected in 3 days. Graft rejection was characterized by microvascular thrombosis and extensive deposition of Ab and complement in the grafts, consistent with AMR. Anti-C5 administration completely blocked terminal complement activity and local C5 deposition, and in combination with cyclosporine and short-term cyclophosphamide treatment, it effectively prevented heart graft rejection. These recipients achieved permanent graft survival for &amp;gt;100 days with normal histology despite the presence of systemic and intragraft anti-donor Abs and complement, suggesting ongoing accommodation. Furthermore, double-transplant experiments demonstrated that immunological alterations in both the graft and the recipient were required for successful graft accommodation to occur. These data suggest that terminal complement blockade with a functionally blocking Ab represents a promising therapeutic approach to prevent AMR in presensitized recipients.<\/jats:p>","DOI":"10.4049\/jimmunol.179.7.4451","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T18:54:06Z","timestamp":1397847246000},"page":"4451-4463","source":"Crossref","is-referenced-by-count":100,"title":["Inhibition of Terminal Complement Components in Presensitized Transplant Recipients Prevents Antibody-Mediated Rejection Leading to Long-Term Graft Survival and Accommodation"],"prefix":"10.1093","volume":"179","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Multi-Organ Transplant Program, University Hospital, London Health Sciences Centre , London, Ontario ,","place":["Canada"]},{"name":"Department of Surgery, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Department of Microbiology and Immunology, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Transplantation, Immunity and Regenerative Medicine, Lawson Health Research Institute, London Health Sciences Centre , London, Ontario ,","place":["Canada"]},{"name":"Department of Pathology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Arp","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J","family":"Faas","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals , Cheshire, CT 06410"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Gies","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals , Cheshire, CT 06410"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"Ramcharran","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertha","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zhong","sequence":"additional","affiliation":[{"name":"Multi-Organ Transplant Program, University Hospital, London Health Sciences Centre , London, Ontario ,","place":["Canada"]},{"name":"Department of Surgery, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Department of Microbiology and Immunology, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Transplantation, Immunity and Regenerative Medicine, Lawson Health Research Institute, London Health Sciences Centre , London, Ontario ,","place":["Canada"]},{"name":"Department of Pathology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P","family":"Rother","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals , Cheshire, CT 06410"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,10,1]]},"reference":[{"key":"2026012810585865500_R1","first-page":"758","volume-title":"Am. 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