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儿童肝移植免疫耐受的研究进展

周艾炜, 刘源, 薛峰, 等. 儿童肝移植免疫耐受的研究进展[J]. 器官移植, 2022, 13(3): 288-295. doi: 10.3969/j.issn.1674-7445.2022.03.002
引用本文: 周艾炜, 刘源, 薛峰, 等. 儿童肝移植免疫耐受的研究进展[J]. 器官移植, 2022, 13(3): 288-295. doi: 10.3969/j.issn.1674-7445.2022.03.002
Zhou Aiwei, Liu Yuan, Xue Feng, et al. Research progress on immune tolerance after pediatric liver transplantation[J]. ORGAN TRANSPLANTATION, 2022, 13(3): 288-295. doi: 10.3969/j.issn.1674-7445.2022.03.002
Citation: Zhou Aiwei, Liu Yuan, Xue Feng, et al. Research progress on immune tolerance after pediatric liver transplantation[J]. ORGAN TRANSPLANTATION, 2022, 13(3): 288-295. doi: 10.3969/j.issn.1674-7445.2022.03.002

儿童肝移植免疫耐受的研究进展

doi: 10.3969/j.issn.1674-7445.2022.03.002
基金项目: 

国家自然科学基金 82000586

国家自然科学基金 82170669

详细信息
    作者简介:
    通讯作者:

    薛峰, Email: fengxue6879@163.com

  • 中图分类号: R617, R318.06

Research progress on immune tolerance after pediatric liver transplantation

More Information
  • 摘要: 肝移植术后免疫耐受是指在肝移植受者中通过各种方式停用免疫抑制剂,且受者肝功能长期维持稳定。目前,实现免疫耐受的方法包括被动免疫耐受、主动操作性免疫耐受和诱导性免疫耐受,多项临床试验证明了其安全性和可行性。相比成人,儿童肝移植受者具有更好的免疫耐受潜质,特别是活体肝移植受者,但预测个体能否达到免疫耐受仍是一大挑战。本文总结了儿童受者免疫耐受的特点、免疫耐受的诱导、操作性免疫耐受、诱导性免疫耐受及受者筛选与耐受标志物的相关研究进展,以期为儿童肝移植术后免疫抑制剂方案的制定提供参考,从而降低患儿的免疫抑制剂总体暴露量,减少免疫抑制剂相关不良反应。

     

  • 表  1  操作性免疫耐受与诱导性免疫耐受临床试验进展

    Table  1.   Progress in clinical trials of operational immune tolerance and induced immune tolerance

    研究者 年份 临床试验类型 例数(n 移植物来源 受者 进展
    Feng S, et al[25-26] 2012、2017 操作性耐受 20 LD 儿童 12例(60%)例耐受,2例(10%)发生排斥反应,5例(25%)例疑似发生排斥反应
    Mazariegos GV, et al[41] 1997 操作性耐受 95 DD 儿童、成人 18例(19%)耐受,18例(19%)发生排斥反应
    Devlin J, et al[42] 1998、2005 操作性耐受 18 DD 成人 2例(11%)耐受,7例(39%)发生排斥反应
    Takatsuki M, et al[43] 2001 操作性耐受 26 LD 儿童 6例(23%)耐受,4例(15%)发生排斥反应
    Oike F, et al[44] 2002 操作性耐受 115 LD 儿童 49例(43%)耐受,20例(17%)发生排斥反应
    Eason JD, et al[45] 2005 操作性耐受 18 - 成人 1例(6%)耐受,11例(61%)发生排斥反应
    Tryphonopoulos P, et al[46-47] 2005、2010 操作性耐受 104 DD 成人 23例(22%)耐受,71例(68%)发生排斥反应
    Tisone G, et al[48], Orlando G, et al[49] 2006、2008 操作性耐受 34 DD 成人 7例(20%)耐受,26例(76%)发生排斥反应
    Assy N, et al[50] 2007 操作性耐受 26 DD 成人 2例(8%)耐受,15例(58%)发生排斥反应
    Pons JA, et al[51] 2009 操作性耐受 20 DD 成人 8例(40%)耐受,6例(30%)发生排斥反应
    de la Garza RG, et al[52] 2013 操作性耐受 24 DD 成人 15例(63%)耐受,2例(8%)发生排斥反应
    Lin NC, et al[53] 2015 操作性耐受 16 LD+DD 儿童 5例(31%)耐受,6例(38%)发生排斥反应
    Levitsky J, et al[54] 2019 操作性耐受 15 LD+DD 成人 8例(53%)耐受,6例(40%)发生排斥反应
    Benítez C, et al[55] 2012 操作性耐受 98 - 成人 41例(42%)耐受,57例(58%)发生排斥反应
    Jucaud V, et al[56] 2019 操作性耐受 31 - 成人 9例(29%)耐受,13例(42%)发生排斥反应
    Shaked A, et al[57] 2019 操作性耐受 77 DD 成人 10例(13%)耐受,32例(42%)发生排斥反应
    Popp FC, et al[58] 2011 诱导性耐受-MSC 3 DD 成人 未见不良反应
    Detry O, et al[59] 2012 诱导性耐受-MSC 10 DD 成人 未见治疗相关不良反应,未见耐受形成
    Zhang YC, et al[60] 2013 诱导性耐受-MSC 12 - 成人 未见治疗相关不良反应,移植物存活率更高
    Zhang Q, et al 2013 诱导性耐受-MSC 210 - 成人 进行中(NCT01844063)
    Yang Y, et al 2014 诱导性耐受-MSC 15 - 成人 进行中(NCT02706132)
    Lorini M, et al 2014 诱导性耐受-MSC 20 - 成人 进行中(NCT02260375)
    Soeder Y, et al[61] 2015 诱导性耐受-MSC 1 LD 成人 未见治疗相关不良反应
    Gubenko Y, et al 2015 诱导性耐受-MSC 35 LD 成人 进行中(NCT02557724)
    Shi M, et al[62] 2017 诱导性耐受-MSC 13 DD 成人 未见治疗相关不良反应,见ALT降低、Treg/Th17比例增高
    Todo S, et al[31] 2010 诱导性耐受-Treg 10 LD 成人 未见治疗相关不良反应,7例完全撤药,3例撤药过程中发生排斥反应
    Lu L, et al 2014 诱导性耐受-Treg 1 LD - 进行中(NCT01624077)
    Feng S, et al 2016 诱导性耐受-Treg 14 LD 成人 进行中(NCT02474199)
    Curry M, et al 2016 诱导性耐受-白细胞介素2 7 - 成人 进行中(NCT02739412)
    Thomson AW, et al 2017 诱导性耐受-DCreg 15 LD 成人 进行中(NCT03164265)
    注:LD为活体肝移植。
           DD为尸体肝移植。
           -为无数据。
           ALT为丙氨酸转氨酶。
           Th17为辅助性T细胞17。
           为正在进行中,可通过临床研究数据库查询[63]
    下载: 导出CSV
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出版历程
  • 收稿日期:  2022-01-18
  • 网络出版日期:  2022-04-29
  • 刊出日期:  2022-05-15

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