Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability.
Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability.
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DOI：
10.1097/txd.0000000000000713
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发表时间：
2017-08
影响因子：
2.3
通讯作者：
Kamei T
中科院分区：
文献类型：
--
作者：
Tokodai K;Miyagi S;Nakanishi C;Hara Y;Nakanishi W;Goto M;Unno M;Kamei T
在儿科患者中，肝移植（LT）后的长期免疫抑制通常是最小的。然而，移植后供体特异性HLA抗体（DSA）可能在这些条件下普遍存在。在这里，我们评估了最小化的钙调磷酸酶抑制剂（CNI）对DSA发展的影响，以评估最小化/撤销免疫抑制的有效性。我们回顾性研究了1991年7月至2013年10月期间在我们机构接受儿科LT的66例患者。根据CNI谷水平将患者分为2组。他克莫司和环孢素的截止谷浓度分别为3和30 ng/mL。进行Luminex单抗原珠测定，并将阳性反应的截止值设定为平均荧光强度（MFI）至少为1000。低CNI组和常规CNI组LT时的平均受体年龄分别为29.1和77.2个月（P = 0.0007）。单因素Logistic回归分析显示，受体年龄小于3岁（P = 0.0099）和低CNI（P < 0.0001）与DSA发展显著相关。在多因素分析中，低CNI是DSA发展的独立危险因素（P = 0.0011）。在15例高MFI DSA中，3例为抗DR，12例为抗DQ。3种抗DR DSA中2种和12种抗DQ DSA中11种具有补体结合能力和高MFI。CNI最小化是儿科LT后长期随访期间移植后DSA的独立风险因素。将CNI调整至适当水平是预防DSA免疫效应的安全第一步。
In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression. We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013. Patients were divided into 2 groups based on the CNI trough level. The cutoff trough levels were 3 and 30 ng/mL for tacrolimus and cyclosporine, respectively. Luminex single-antigen bead assays were performed, and the cutoff for a positive reaction was set at a mean fluorescence intensity (MFI) of at least 1000. The mean recipient ages at the time of LT were 29.1 and 77.2 months for the low and regular CNI groups, respectively (P = 0.0007). Univariate logistic regression analysis revealed that recipient age at LT younger than 3 years (P = 0.0099) and low CNI (P < 0.0001) were significantly associated with DSA development. In multivariate analysis, low CNI was an independent risk factor of DSA development (P = 0.0011). Of 15 high-MFI DSAs, 3 were anti-DR, and 12 were anti-DQ. Two of 3 anti-DR DSAs and 11 of 12 anti-DQ DSAs had complement-binding ability and high MFIs. CNI minimization was an independent risk factor for posttransplant DSA during long-term follow-up after pediatric LT. Adjusting CNI to appropriate levels is a safe first step to prevent the immunological effects of DSA.