title: Complement inhibition enables renal allograft accommodation and long-term engraftment in presensitized nonhuman primates.
abstract: Protection against humoral injury mediated by donor-specific antibodies (DSA), also known as accommodation, may allow for long-term allograft survival in presensitized recipients. In the present study, we determined the role of complement in renal allograft accommodation in donor skin-presensitized nonhuman primates under conventional immunosuppression. Donor skin allografts were transplanted to presensitized recipients 14 days prior to renal transplantation. Renal allografts not receiving any immunosuppressive treatment developed accelerated rejection with predominantly humoral injury, which was not prevented using conventional cyclosporine (CsA) triple therapy. Inhibition of complement activation with the Yunnan-cobra venom factor (Y-CVF) successfully prevented accelerated antibody-mediated rejection and resulted in successful accommodation and long-term renal allograft survival in most presensitized recipients. Accommodation in this model was associated with the prevention of the early antibody responses induced against donor antigens by complement inhibition. Some antiapoptotic proteins and complement regulatory proteins, including Bcl-2, CD59, CD46 and clusterin, were upregulated in the surviving renal allografts. These results suggest that the complement inhibition-based strategy may be valuable alternative in future clinical cross-match positive or ABO-incompatible transplantation.
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen Song
authors.forename: S
authors.initials: S
authors.lastname: Zhong
authors.forename: Y
authors.initials: Y
authors.lastname: Xiang
authors.forename: J-H
authors.initials: JH
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: W-Y
authors.initials: WY
authors.lastname: Wang
authors.forename: Y-L
authors.initials: YL
authors.lastname: Xiong
authors.forename: X-C
authors.initials: XC
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Chen Shi
authors.forename: X-P
authors.initials: XP
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000187:drug effects; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation; D011323:Primates; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D003165:Complement System Proteins