Mendoza Rojas Aleixandra, Verhoeven Jeroen G H P, de Kuiper Ronella, Clahsen-van Groningen Marian C, Boer Karin, Hesselink Dennis A, van Gelder Teun, van Besouw Nicole M, Baan Carla C
Department of Internal Medicine-Nephrology and Transplantation, Erasmus MC Transplantation Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Internal Medicine, Erasmus MC Transplant Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Transplant Direct. 2023 Apr 20;9(5):e1478. doi: 10.1097/TXD.0000000000001478. eCollection 2023 May.
Memory T cells are important mediators of transplant rejection but are not routinely measured before or after kidney transplantation. The aims of this study were as follows: (1) validate whether pretransplant donor-reactive memory T cells are reliable predictors of acute rejection (AR) (2) determine whether donor-reactive memory T cells can distinguish AR from other causes of transplant dysfunction.
Samples from 103 consecutive kidney transplant recipients (2018-2019) were obtained pretransplantation and at time of for-cause biopsy sampling within 6 mo of transplantation. The number of donor-reactive interferon gamma (IFN-γ) and interleukin (IL)-21-producing memory T cells was analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay.
Of the 63 patients who underwent a biopsy, 25 had a biopsy-proven acute rejection (BPAR; 22 aTCMR and 3 aAMR), 19 had a presumed rejection, and 19 had no rejection. Receiver operating characteristic analysis showed that the pretransplant IFN-γ ELISPOT assay distinguished between patients who later developed BPAR and patients who remained rejection-free (area under the curve [AUC] 0.73; sensitivity 96% and specificity 41%). Both the IFN-γ and IL-21 assays were able to discriminate BPAR from other causes of transplant dysfunction (AUC 0.81; sensitivity 87% and specificity 76% and AUC 0.81; sensitivity 93% and specificity 68%, respectively).
This study validates that a high number of donor-reactive memory T cells before transplantation is associated with the development of AR after transplantation. Furthermore, it demonstrates that the IFN-γ and IL-21 ELISPOT assays are able to discriminate between patients with AR and patients without AR at the time of biopsy sampling.
记忆性T细胞是移植排斥反应的重要介导因子，但在肾移植前后通常不会进行常规检测。本研究的目的如下：（1）验证移植前供体反应性记忆性T细胞是否为急性排斥反应（AR）的可靠预测指标；（2）确定供体反应性记忆性T细胞能否将AR与移植功能障碍的其他原因区分开来。
收集了103例连续肾移植受者（2018 - 2019年）移植前及移植后6个月内因病因进行活检时的样本。通过酶联免疫斑点（ELISPOT）试验分析供体反应性干扰素γ（IFN-γ）和产生白细胞介素（IL）-21的记忆性T细胞数量。
在63例接受活检的患者中，25例经活检证实为急性排斥反应（BPAR；22例抗体介导的急性细胞排斥反应和3例急性抗体介导排斥反应），19例为疑似排斥反应，19例无排斥反应。受试者操作特征分析表明，移植前IFN-γ ELISPOT试验能够区分后来发生BPAR的患者和未发生排斥反应的患者（曲线下面积[AUC]为0.73；敏感性为96%，特异性为41%）。IFN-γ和IL-21试验均能够将BPAR与移植功能障碍的其他原因区分开来（AUC分别为0.81；敏感性为87%，特异性为76%和AUC为0.81；敏感性为93%，特异性为68%）。
本研究证实移植前大量供体反应性记忆性T细胞与移植后AR的发生有关。此外，研究表明在活检取样时，IFN-γ和IL-21 ELISPOT试验能够区分有AR的患者和无AR的患者。
