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肾移植受者输注供体骨髓细胞的五年临床效果:改善移植肾功能并提高移植肾存活率。

Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients: improved graft function and higher graft survival.

作者信息

Solgi Ghasem, Gadi Vijayakrishna, Paul Biswajit, Mytilineos Joannis, Pourmand Gholamreza, Mehrsai Abdolrasoul, Ranjbar Moslem, Mohammadnia Mousa, Nikbin Behrouz, Amirzargar Ali Akbar

机构信息

Immunology Department; School of Medicine; Hamadan University of Medical Sciences; Hamadan, Iran.

出版信息

Chimerism. 2013 Jul-Sep;4(3):87-94. doi: 10.4161/chim.24719. Epub 2013 May 31.

DOI:10.4161/chim.24719
PMID:23639966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3782550/
Abstract

Augmentation of microchimerism in solid organ transplant recipients by donor bone marrow cells (DBMC) infusion may promote immune hyporesponsiveness and consequently improve long-term allograft survival. Between March 2005 and July 2007, outcomes for 20 living unrelated donor (LURD) primary kidney recipients with concurrent DBMC infusion (an average of 2.19 ± 1.13 x 10⁹ donor cells consisting of 2.66 ± 1.70 x 10⁷ CD34⁺ cells) were prospectively compared with 20 non-infused control allograft recipients given similar conventional immunosuppressive regimens. With five years of clinical follow up, a total of 11 cases experienced rejection episodes (3 DBMI patients vs. 8 controls, p = 0.15). One DBMC-infused patient experienced chronic rejection vs. two episodes (1 biopsy-confirmed) in the control patients. Actuarial and death-censored 5-y graft survival was significantly higher in infused patients compared with controls (p = 0.01 and p = 0.03, respectively). Long-term graft survival was significantly associated with pre-transplant anti-HLA antibodies (p = 0.01), slightly with peripheral microchimerism (p = 0.09) and CD4⁺CD25⁺FoxP3⁺ T cells (p = 0.09). Immunosuppressant dosing was lower in infused patients than controls, particularly for mycophenolate mofetil (p = 0.001). The current findings as well as our previous reports on these patients indicates clinical improvement in long-term graft survival of renal transplant patients resulting from low-dose DBMC infusion given without induction therapy.

摘要

通过输注供体骨髓细胞(DBMC)增强实体器官移植受者体内的微嵌合现象,可能会促进免疫低反应性,从而提高长期移植器官的存活率。在2005年3月至2007年7月期间,对20例接受同期DBMC输注的活体非亲属供体(LURD)原发性肾移植受者(平均输入2.19±1.13×10⁹个供体细胞,其中包括2.66±1.70×10⁷个CD34⁺细胞)的预后,与20例接受类似传统免疫抑制方案但未输注DBMC的对照移植受者进行了前瞻性比较。经过五年的临床随访,共有11例患者发生排斥反应(3例输注DBMC患者与8例对照患者,p = 0.15)。1例输注DBMC的患者发生慢性排斥反应,而对照患者中有2例发生(1例经活检证实)。与对照组相比,输注患者的精算和死亡校正5年移植存活率显著更高(分别为p = 0.01和p = 0.03)。长期移植存活率与移植前抗HLA抗体显著相关(p = 0.01),与外周微嵌合现象轻度相关(p = 0.09),与CD4⁺CD25⁺FoxP3⁺ T细胞也轻度相关(p = 0.09)。输注患者的免疫抑制剂剂量低于对照组,尤其是霉酚酸酯(p = 0.001)。目前的研究结果以及我们之前关于这些患者的报告表明,在不进行诱导治疗的情况下给予低剂量DBMC输注,可使肾移植患者的长期移植存活率得到临床改善。

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本文引用的文献

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Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.可溶性 CD30 与临床而非亚临床肾移植排斥反应相关。
Transpl Int. 2013 Jan;26(1):75-83. doi: 10.1111/j.1432-2277.2012.01578.x. Epub 2012 Nov 8.
2
Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.移植前可溶性 CD30 水平作为肾移植急性排斥反应的预测因子:一项荟萃分析。
Transplantation. 2012 Nov 15;94(9):911-8. doi: 10.1097/TP.0b013e31826784ad.
3
Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial.供体来源的外周血单个核细胞DNA与肾移植稳定功能相关:一项随机对照试验。
Chimerism. 2011 Oct-Dec;2(4):102-10. doi: 10.4161/chim.2.4.19095.
4
The impact of donor-specific anti-HLA antibodies on late kidney allograft failure.供者特异性抗 HLA 抗体对晚期肾移植失败的影响。
Nat Rev Nephrol. 2012 Apr 17;8(6):348-57. doi: 10.1038/nrneph.2012.81.
5
Regulatory T-cell subset analysis and profile of interleukin (IL)-10, IL-17 and interferon-gamma cytokine-producing cells in kidney allograft recipients with donor cells infusion.供者细胞输注的肾移植受者调节性 T 细胞亚群分析及白细胞介素-10、白细胞介素-17 和干扰素-γ细胞因子产生细胞的特征。
Clin Exp Nephrol. 2012 Aug;16(4):636-46. doi: 10.1007/s10157-012-0591-9.
6
Clinical relevance of pre and post-transplant immune markers in kidney allograft recipients: anti-HLA and MICA antibodies and serum levels of sCD30 and sMICA.移植前和移植后免疫标志物在肾移植受者中的临床意义:抗 HLA 和 MICA 抗体以及血清 sCD30 和 sMICA 水平。
Transpl Immunol. 2012 Mar;26(2-3):81-7. doi: 10.1016/j.trim.2011.12.002. Epub 2011 Dec 13.
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Serum levels of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-β1, and interferon-γ cytokines and expression levels of IL-10 and TGF-β1 genes in renal allograft recipients after donor bone marrow cell infusion.
Transplant Proc. 2011 Mar;43(2):495-9. doi: 10.1016/j.transproceed.2011.01.005.
8
Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion.接受供体骨髓细胞输注的受者中抗HLA抗体与肾移植结果
Iran J Immunol. 2010 Mar;7(1):18-29.
9
Should microchimerism turn into rejection prophylactics?微小嵌合体是否会变成排斥预防措施?
Expert Rev Mol Diagn. 2010 Jan;10(1):107-18. doi: 10.1586/erm.09.79.
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TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.接受供体骨髓细胞输注的肾移植患者的TH1/TH2细胞因子和可溶性CD30水平
Transplant Proc. 2009 Sep;41(7):2800-4. doi: 10.1016/j.transproceed.2009.07.053.