Triptolide inhibits donor-specific antibody production and attenuates mixed antibody-mediated renal allograft injury.

Abstract

Donor-specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSAs are important in promoting long-term graft survival. Triptolide exhibits a wide spectrum of antiinflammatory and immunosuppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of DSAs in transplant recipients. We found that triptolide treatment of skin allograft recipients in mice significantly suppressed the development of circulating anti-donor-specific IgG and effectively alleviated DSA-mediated renal allograft injury, which led to prolonged allograft survival. In vitro studies revealed that triptolide inhibited the differentiation of B cells into CD138+ CD27++ plasma cells; reduced the levels of IgA, IgG, and IgM secreted by plasma cells; and repressed somatic hypermutation and class switch recombination of B cells. Moreover, triptolide-treated recipients showed reduced numbers of B cells, plasma cells, and memory B cells in spleens and decreased numbers of T, B, natural killer (NK) cells, and macrophages infiltrating grafts. These findings highlight the importance of triptolide in suppressing DSAs and establish triptolide as a novel therapeutic agent for antibody-mediated allograft rejection.

• Authors: Daqiang Zhao, Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 18 Issue 5 Pg. 1083-1095 (05 2018) ISSN: 1600-6143 [Electronic] United States
• PMID: 29178433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Diterpenes
• Epoxy Compounds
• Immunosuppressive Agents
• Isoantibodies
• Phenanthrenes
• triptolide

Topics

• Allografts
• Animals
• B-Lymphocytes (drug effects, immunology)
• Diterpenes (therapeutic use)
• Epoxy Compounds (therapeutic use)
• Graft Rejection (drug therapy, etiology, pathology)
• Graft Survival (drug effects, immunology)
• Immunosuppressive Agents (therapeutic use)
• Inflammation (drug therapy, etiology, pathology)
• Isoantibodies (drug effects, immunology)
• Kidney Transplantation (adverse effects)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Phenanthrenes (therapeutic use)
• Tissue Donors