Inhibition of Terminal Complement Components in Presensitized Transplant Recipients Prevents Antibody-Mediated Rejection Leading to Long-Term Graft Survival and Accommodation

摘要: 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 early graft loss. Complement plays an important role process of AMR. In present study, a murine model was designed mimic AMR patients. This used evaluate effect blocking fifth complement component (C5) with anti-C5 mAb on prevention rejection. BALB/c recipients were C3H donor skin grafts 7 days before heart transplantation from same strain. Heart grafts, transplanted when circulating anti-donor IgG Abs at peak levels, rejected 3 days. Graft characterized by microvascular thrombosis extensive deposition Ab consistent Anti-C5 administration completely blocked terminal activity local C5 deposition, combination cyclosporine short-term cyclophosphamide treatment, effectively prevented These achieved permanent survival for >100 normal histology despite presence systemic intragraft complement, suggesting ongoing accommodation. Furthermore, double-transplant experiments demonstrated that immunological alterations both recipient required successful accommodation occur. data suggest blockade functionally represents promising therapeutic approach prevent recipients.