Induction of Accommodation by Anti–complement Component 5 Antibody-based Immunosuppression in ABO-incompatible Heart Transplantation. Issue 9 (September 2019)

• Record Type: Journal Article
• Authors: Park, Sunjoo; Lee, Jae-Ghi; Jang, Joon Young; Ryu, Jung-Hwa; Kim, Dong jo; Chang, Shin Jae; Kim, Hyori; Chung, Junho; West, Lori; Yang, Jaeseok
• Is Part Of: Transplantation. Volume 103:Issue 9(2019)
• Publication Date: 2019-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000002808
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: Plasmapheresis in combination with immunoglobulin and rituximab is often used to induce accommodation in ABO-incompatible (ABOi) living-donor transplantation; however, this regimen cannot be applied to cases of ABOi deceased-donor transplantation. Here, we investigated whether an anti–complement component 5 (C5) antibody-based regimen can induce accommodation in ABOi heart transplantation. Methods: Both IgM and IgG anti-blood type A antibodies were induced in wild-type mice by sensitization using human blood type A antigen. Heterotopic ABOi heart transplantation was performed from human blood type A-transgenic C57BL/6J mice to sensitized wild-type DBA/2 mice. Results: Either anti-C5 antibody or conventional triple immunosuppressants (corticosteroid, tacrolimus, mycophenolate mofetil) alone did not induce accommodation in majority of ABOi heart allografts, whereas their combination induced accommodation in more than 70% of cases despite the presence of anti-A antibodies. The combination therapy markedly suppressed the infiltration of T cells and macrophages into ABOi allografts, despite mild deposition of IgG and C4d. T-cell activation and differentiation into Th1, Th2, and Th17 cells were suppressed along with CD49d high CD4 + T and follicular helper T cells in the combination treatment group. CD24 + B cells, including both CD24 + CD23 + marginal zone B cells and CD24 + CD23 − T2-marginal zone B cells, were increased in the accommodation group. Conclusions: C5 inhibitor-based immunosuppression induced accommodation in murine ABOi heart transplantation, presenting a promising strategy for ABOi deceased-donor transplantation. Abstract : Supplemental Digital Content is available in the text.