期刊
TRANSPLANTATION
卷 102, 期 7, 页码 1075-1084出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0000000000002204
关键词
-
资金
- ISCIII-Subdireccion General de Evaluacion [PI11/01112]
- Redes Tematicas De Investigacion Cooperativa En Salud, REDINREN - ISCIII-Subdireccion General de Evaluacion [RD12/0021/0028, RD16/0009/0023]
- Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa
Background The progression from acute to chronic antibody-mediated rejection in kidney transplant recipients is usually not prevented by current therapeutic options. Here, we investigated whether the use of tofacitinib (TOFA), a Janus kinase 3 inhibitor, was capable of preventing the progression of allograft dysfunction in a Fisher-to-Lewis rat model of kidney transplantation. Methods Rats were treated from the third week after transplantation to allow the development of rejection. Treatment was based on cyclosporin A, rapamycin or TOFA. Renal function was assessed at 1, 4, 8, and 12 weeks after transplantation, whereas rat survival, histological lesions, and infiltrating lymphocytes were analyzed at 12 weeks. Results Tofacitinib prolonged graft survival, preserved tubular and glomerular structures and reduced humoral damage characterized by C4d deposition. Tofacitinib was able to reduce donor-specific antibodies. In addition, T and natural killer cell graft infiltration was reduced in TOFA-treated rats. Although rapamycin-treated rats also showed prolonged graft survival, glomerular structures were more affected. Moreover, only TOFA treatment reduced the presence of T, B and natural killer cells in splenic parenchyma. Conclusions Tofacitinib is able to reduce the immune response generated in a rat model of kidney graft rejection, providing prolonged graft and recipient survival, better graft function, and less histological lesions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据