Brigham and Women's Hospital, Transplantation Research Center, 221 Longwood Ave, 3rd Floor, Boston, MA 02115, USA.
J Am Soc Nephrol. 2012 Jan;23(1):174-82. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3.
The incidence of developing circulating anti-human leukocyte antigen antibodies and the kinetics of T cell depletion and recovery among pediatric renal transplant recipients who receive alemtuzumab induction therapy are unknown. In a collaborative endeavor to minimize maintenance immunosuppression in pediatric renal transplant recipients, we enrolled 35 participants from four centers and treated them with alemtuzumab induction therapy and a steroid-free, calcineurin-inhibitor-withdrawal maintenance regimen. At 3 months after transplant, there was greater depletion of CD4(+) than CD8(+) T cells within the total, naive, memory, and effector memory subsets, although depletion of the central memory subset was similar for CD4(+) and CD8(+) cells. Although CD8(+) T cells recovered faster than CD4(+) subsets overall, they failed to return to pretransplant levels by 24 months after transplant. There was no evidence for greater recovery of either CD4(+) or CD8(+) memory cells than naïve cells. Alemtuzumab relatively spared CD4(+)CD25(+)FoxP3(+) regulatory T cells, resulting in a rise in their numbers relative to total CD4(+) cells and a ratio that remained at least at pretransplant levels throughout the study period. Seven participants (20%) developed anti-human leukocyte antigen antibodies without adversely affecting allograft function or histology on 2-year biopsies. Long-term follow-up is underway to assess the potential benefits of this regimen in children.
接受阿仑单抗诱导治疗的儿科肾移植受者体内循环抗人白细胞抗原抗体的发生率以及 T 细胞耗竭和恢复的动力学尚不清楚。为了尽量减少儿科肾移植受者的维持性免疫抑制,我们开展了一项合作研究,共纳入了来自四个中心的 35 名患者,对他们采用阿仑单抗诱导治疗和不含激素的钙调磷酸酶抑制剂停药维持方案。移植后 3 个月,在总 T 细胞、幼稚 T 细胞、记忆 T 细胞和效应记忆 T 细胞亚群中,CD4(+)T 细胞的耗竭程度大于 CD8(+)T 细胞,尽管 CD4(+)和 CD8(+)细胞的中央记忆 T 细胞亚群的耗竭程度相似。尽管 CD8(+)T 细胞的恢复速度总体上快于 CD4(+)细胞亚群,但到移植后 24 个月时仍未恢复到移植前的水平。无论是 CD4(+)还是 CD8(+)记忆 T 细胞,其恢复程度均未超过幼稚 T 细胞。阿仑单抗相对保留了 CD4(+)CD25(+)FoxP3(+)调节性 T 细胞,导致其数量相对于总 CD4(+)细胞增加,而且在整个研究期间,其比例至少保持在移植前的水平。7 名患者(20%)出现了抗人白细胞抗原抗体,但并未对移植后 2 年的活检样本中的移植物功能或组织学产生不良影响。目前正在进行长期随访,以评估该方案在儿童中的潜在益处。