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围手术期最小诱导治疗:移植中更有效免疫抑制的进一步举措。

Perioperative Minimal Induction Therapy: A Further Step toward More Effective Immunosuppression in Transplantation.

作者信息

Gennarini Alessia, Cravedi Paolo, Marasà Maddalena, Perna Annalisa, Rota Giovanni, Bontempelli Mario, Sandrini Silvio, Remuzzi Giuseppe, Ruggenenti Piero

机构信息

Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano, 87, 24126 Bergamo, Italy.

出版信息

J Transplant. 2012;2012:426042. doi: 10.1155/2012/426042. Epub 2012 May 20.

DOI:10.1155/2012/426042
PMID:22685630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3364007/
Abstract

Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5 mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20 mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens.

摘要

低剂量兔抗人胸腺细胞球蛋白(RATG)与巴利昔单抗联合诱导治疗能有效且安全地预防高危肾移植受者的移植物排斥反应。为评估治疗时机是否会影响疗效和耐受性,在这项单中心、匹配队列研究中,我们比较了25例患者与50例性别、年龄及治疗相匹配的对照患者的移植后结局,这两组患者分别在植入前或植入后接受相同疗程的每日7次RATG输注(0.5mg/kg/天)。所有受试者在移植前及移植后4天接受巴利昔单抗(20mg)治疗,术后6天内停用类固醇,并采用环孢素和霉酚酸酯或硫唑嘌呤进行无类固醇免疫抑制维持治疗。移植后12个月内,1例患者(4%)和13例对照患者(26%)发生急性排斥反应。1例患者和5例对照患者因移植肾功能延迟恢复需要透析治疗。所有患者在植入前循环中的CD4+和CD8+T淋巴细胞均被完全清除。两种治疗方法耐受性均良好。在肾移植中,围手术期输注RATG可增强低剂量RATG和巴利昔单抗诱导治疗对移植物排斥反应和肾功能延迟恢复的保护作用,这可能是因为能更有效地抑制循环T细胞与移植物抗原之间的早期相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28c0/3364007/e32dc1eba16e/JTRAN2012-426042.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28c0/3364007/2f0f3b74ff36/JTRAN2012-426042.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28c0/3364007/e32dc1eba16e/JTRAN2012-426042.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28c0/3364007/2f0f3b74ff36/JTRAN2012-426042.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28c0/3364007/e32dc1eba16e/JTRAN2012-426042.002.jpg

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本文引用的文献

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Immune reconstitution following rabbit antithymocyte globulin.兔抗胸腺细胞球蛋白治疗后的免疫重建。
Am J Transplant. 2010 Sep;10(9):2132-2141. doi: 10.1111/j.1600-6143.2010.03210.x.
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Polyclonal rabbit antithymocyte globulin exhibits consistent immunosuppressive capabilities beyond cell depletion.多克隆兔抗胸腺细胞球蛋白除了具有细胞清除作用外,还表现出持续的免疫抑制能力。
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与远程自体间充质基质细胞给药相关的肾移植耐受
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Basiliximab combined with low-dose rabbit anti-human thymocyte globulin: a possible further step toward effective and minimally toxic T cell-targeted therapy in kidney transplantation.巴利昔单抗联合低剂量兔抗人胸腺细胞球蛋白:肾移植中实现有效且低毒的T细胞靶向治疗的可能进一步举措。
Clin J Am Soc Nephrol. 2006 May;1(3):546-54. doi: 10.2215/CJN.01841105. Epub 2006 Mar 1.
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Antithymocyte globulins suppress dendritic cell function by multiple mechanisms.抗胸腺细胞球蛋白通过多种机制抑制树突状细胞功能。
Transplantation. 2007 Feb 27;83(4):485-97. doi: 10.1097/01.tp.0000251975.81281.22.
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Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR Study.肾移植受者中使用霉酚酸酯、达利珠单抗和皮质类固醇减少环孢素用量:CAESAR研究
Am J Transplant. 2007 Mar;7(3):560-70. doi: 10.1111/j.1600-6143.2006.01645.x. Epub 2007 Jan 22.
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Rabbit antithymocyte globulin versus basiliximab in renal transplantation.兔抗胸腺细胞球蛋白与巴利昔单抗在肾移植中的比较
N Engl J Med. 2006 Nov 9;355(19):1967-77. doi: 10.1056/NEJMoa060068.
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A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells.抗胸腺细胞球蛋白的一种新作用机制:诱导CD4+CD25+Foxp3+调节性T细胞。
J Am Soc Nephrol. 2006 Oct;17(10):2844-53. doi: 10.1681/ASN.2006050422. Epub 2006 Aug 16.