Triptolide Alleviating Acute Antibody Mediated Rejection by Inhibition of B Cell Activation in Presensitized Recipients.
1Kidney Transplantation, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
2Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
Meeting: 2017 American Transplant Congress
Abstract number: C6
Keywords: Antibodies, Kidney transplantation, Mice, Rejection
Session Information
Session Name: Poster Session C: Antibody and B Cell
Session Type: Poster Session
Date: Monday, May 1, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Backgroud: Acute antibody mediated rejection (AMR), resistant to most anti-rejection therapy, is main cause for renal graft loss. Triptolide(TPL) had been reported as a promising agent in treating antibody involved nephropathy of IgA and lupus, which showed inhibition effects on IgA and anti-dsDNA antibody development. In this study,we revealed an unexpected effects of TPL in preventing AMR in kidney transplantation. Methods:6-8 weeks male C3H and Balb/c mice were used as donors and recipients of skin or kidney transplantation. Kidney transplantations were performed after 4 days of pre-sensitization by skin transplantations to establish a mouse acute AMR model. Recipients were divided into 4 groups:(1)TPL-ST group, mouse received skin graft sensitization without receiving subsequent kidney graft, TPL-prodrug of MC002 was administrated from day of skin transplantation to 30 days; (2) non-TPL-ST control group; (3)TPL-AMR group, MC002 was administrated from day of skin transplantation to kidney transplantation; (4) non-TPL-AMR control group. Normal saline was injected in control groups. Results:TPL-ST decreased 50% of circulating donor specific antibody (DSA) levels in skin pre-sensitization period (p<0.01). In-vitro study showed that TPL significantly inhibited B cells from differentiation into plasma B cells and reduced immunoglobulins production of Ig A, IgG and IgM (p<0.01). In-vivo study showed TPL prolonged TPL-AMR group 2 days of medium survival time compared with non-TPL-AMR group. Histological analysis on day 5 after kidney transplantation demonstrated alleviation of AMR injuries in TPL-AMR group. TPL significantly reduced B cells, B memory cells and plasma B cells populations in spleen compared with non-TPL-AMR group(p<0.01). This inhibition of B cells was accompanied by decreased T cells and Macrophage cells infiltration in grafts. Conclusions:Our results showed that TPL alleviated AMR injuries by inhibition of B cell activation during pre-sensitization stage. Its inhibitive effects on B cells activation and DSA development indicates the clinical value of TPL in preventing AMR in kidney transplantation.
CITATION INFORMATION: Zhao D, Li S, Liao T, Wei Y, Hua X, Han F, Luo Z, Liu X, Sun Q. Triptolide Alleviating Acute Antibody Mediated Rejection by Inhibition of B Cell Activation in Presensitized Recipients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Zhao D, Li S, Liao T, Wei Y, Hua X, Han F, Luo Z, Liu X, Sun Q. Triptolide Alleviating Acute Antibody Mediated Rejection by Inhibition of B Cell Activation in Presensitized Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/triptolide-alleviating-acute-antibody-mediated-rejection-by-inhibition-of-b-cell-activation-in-presensitized-recipients/. Accessed May 12, 2025.« Back to 2017 American Transplant Congress