Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.
Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany.
Transpl Int. 2020 Mar;33(3):288-297. doi: 10.1111/tri.13551. Epub 2019 Nov 26.
Preformed donor-reactive T cells are relatively resistant to standard immunosuppression and account for an increased incidence of T cell-mediated rejection (TCMR) and inferior kidney allograft outcomes. We analyzed 150 living donor kidney transplant recipients (KTRs) of a first kidney allograft. Ninety-eight ABO-compatible (ABOc) and 52 ABO-incompatible (ABOi) KTRs were included. Samples were collected at 6 time points, before rituximab, before immunoadsorption and pretransplantation, at +1, +2, and +3 months posttransplantation, and donor-reactive T cells were measured by interferon-γ ELISPOT assay. Twenty of 98 ABOc (20%) and 12 of 52 ABOi KTRs (23%) showed positive pretransplant ELISPOT. Eight of 20 ABOc-KTRs (40%) with positive pretransplant ELISPOT showed TCMR, whereas 17 of 78 ABOc-KTRs (22%) with negative pretransplant ELISPOT did (P = 0.148). Seven of 12 ABOi KTRs (57%) with positive pretransplant ELISPOT showed TCMR, whereas only 3 of 40 ABOi KTRs (8%) with negative pretransplant ELISPOT did (P < 0.001). Interestingly, 6 of 7 ABOi KTRs with positive pretransplant ELISPOT that persists after ABO desensitization developed TCMR. Among 118 KTRs with negative pretransplant ELISPOT, 10 of 72 ABOc-KTRs (14%), but 0 of 46 ABOi KTRs, developed positive posttransplant ELISPOT (P = 0.006). Preformed donor-reactive T cells that persist despite ABO desensitization identify KTRs at highest risk of TCMR. Less de-novo donor-reactive T cells after ABO desensitization may account for less TCMR. Both, the use of rituximab and early initiation of calcineurin inhibitor-based maintenance immunosuppression may contribute to these findings.
预先存在的供体反应性 T 细胞对标准免疫抑制相对耐受，导致 T 细胞介导的排斥反应（TCMR）发生率增加和移植物结局不佳。我们分析了 150 例首次接受肾移植的活体供肾受者（KTR）的资料。其中 98 例 ABO 相容（ABOc）和 52 例 ABO 不相容（ABOi）KTR 入组。样本采集时间点为利妥昔单抗治疗前、免疫吸附治疗前和移植前，以及移植后+1、+2 和+3 个月，通过干扰素-γ ELISPOT 检测供体反应性 T 细胞。98 例 ABOc 中有 20 例（20%）和 52 例 ABOi 中有 12 例（23%）在移植前 ELISPOT 检测中呈阳性。20 例 ABOc-KTR 中有 8 例（40%）移植前 ELISPOT 阳性者发生 TCMR，而 78 例 ABOc-KTR 中有 17 例（22%）移植前 ELISPOT 阴性者发生 TCMR（P=0.148）。12 例 ABOi-KTR 中有 7 例（57%）移植前 ELISPOT 阳性者发生 TCMR，而 40 例 ABOi-KTR 中有 3 例（8%）移植前 ELISPOT 阴性者发生 TCMR（P<0.001）。有趣的是，7 例 ABOi-KTR 移植前 ELISPOT 阳性者在 ABO 脱敏后仍持续存在，其中 6 例发生 TCMR。在 118 例移植前 ELISPOT 阴性的 KTR 中，72 例 ABOc-KTR 中有 10 例（14%），而 46 例 ABOi-KTR 中无一例（P=0.006）发生移植后 ELISPOT 阳性。尽管 ABO 脱敏后仍持续存在的预先存在的供体反应性 T 细胞可识别发生 TCMR 风险最高的 KTR。ABO 脱敏后较少产生新的供体反应性 T 细胞可能与 TCMR 发生率较低有关。利妥昔单抗的使用和钙调磷酸酶抑制剂维持免疫抑制的早期启动可能是这些发现的原因。
