Complement inhibition with an anti-C5 monoclonal antibody prevents hyperacute rejection in a xenograft heart transplantation model

Hao Wang, Scott A. Rollins, Zuhua Gao, Bertha Garcia, Zheng Zhang, Jingjing Xing, Lan Li, Richard Kellersmann, Louis A. Matis, Robert Zhong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Background. The present study was undertaken to determine whether anti- complement 5 (C5) monoclonal antibodies (mAb) prevent hyperacute rejection (HAR) in a rat-to-presensitized mouse heart transplantation model and whether these mAb, combined with cyclosporine (CsA) and cyclophosphamide (CyP), can achieve long-term graft survival. Methods. BALB/c mice were presensitized with 2x107 splenocytes from Lewis rats 14 days before grafting. Heart grafts from Lewis rats were heterotopically transplanted into BALB/c mice. Presensitized mice were treated with either anti-C5 mAb or a combination of anti-C5 mAb, CsA, and CyP. Controls included: presensitized mice with no treatment, presensitized mice treated with either CsA + CyP or IgG, and nonpresensitized mice with either no treatment or with CsA + CyP treatment. Results. Although typical features of HAR were evident in the presensitized grafts, the mAb completely inhibited complement activation and successfully prevented HAR. Despite complement inactivation, the graft was rejected on postoperative day 6 with acute vascular rejection (AVR) also known as delayed xenograft rejection (DXR). Notably, this type of rejection cannot be effectively overcome by CsA and CyP. Conclusions. We conclude that (1) anti- C5 mAb prevents HAR, (2) AVR/DXR still occurs when HAR is prevented by complement inactivation, and (3) AVR/DXR cannot be overcome by conventional immunosuppression. These data suggest that anti-C5 mAb may be valuable for preventing HAR in future clinical xenotransplantation and that additional interventions may be required to address AVR/DXR.

Original languageEnglish (US)
Pages (from-to)1643-1651
Number of pages9
JournalTransplantation
Volume68
Issue number11
DOIs
StatePublished - Dec 15 1999

ASJC Scopus subject areas

  • Transplantation

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