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探索钙调磷酸酶抑制剂-free 维持免疫抑制的肝移植受者中可预测的间接可识别 HLA 表位 (PIRCHE-II)。一项回顾性单中心研究。

Exploring predicted indirectly recognizable HLA epitopes (PIRCHE-II) in liver transplant recipients on calcineurin inhibitor-free maintenance immunosuppression. A retrospective single center study.

机构信息

CHU Saint Eloi, Hepatology and Liver transplantation unit, Montpellier, France.

PIRCHE AG, Berlin, Germany.

出版信息

Transpl Immunol. 2020 Apr;59:101272. doi: 10.1016/j.trim.2020.101272. Epub 2020 Feb 12.

Abstract

The PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) score is an HLA epitope matching algorithm. PIRCHE algorithm estimates the level of presence of T-cell epitopes in mismatched HLA. The PIRCHE-II numbers associate with de novo donor-specific antibody (dnDSA) formation following liver transplantation and kidney allograft survival following renal transplantation. The aim of our study was to assess the PIRCHE-II score in calcineurin inhibitor (CNI)-free maintenance immunosuppression recipients. This was a retrospective study of forty-one liver transplant recipients on CNI-free immunosuppression and with available liver allograft biopsies. Donors and recipients were HLA typed. The HLA-derived mismatched peptide epitopes that could be presented by the recipient's HLA-DRB1 molecules were calculated using PIRCHE-II algorithm. The associations between PIRCHE-II scores and graft immune-mediated events were assessed using receiver operating characteristics curves and subsequent univariate and multivariate analyses. CNI-free patients with cellular rejection, humoral rejection, or severe portal inflammation had higher mean PIRCHE-II scores compared to patients with normal liver allografts. PIRCHE-II score and donor age were independent risk factors for liver graft survival in CNI-free patients (HR: 8.0, 95% CI: 1.3-49, p = .02; and HR: 0.88, 95% CI: 0.00-0.96, p = .007, respectively). PIRCHE-II scores could be predictive of liver allograft survival in CNI-free patients following liver transplantation. Larger studies are needed to confirm these results.

摘要

PIRCHE(预测间接可识别 HLA 表位)评分是一种 HLA 表位匹配算法。PIRCHE 算法估计错配 HLA 中 T 细胞表位的存在水平。PIRCHE-II 数字与肝移植后新的供体特异性抗体(dnDSA)形成和肾移植后肾移植物存活有关。我们的研究目的是评估钙调神经磷酸酶抑制剂(CNI)免费维持免疫抑制治疗患者的 PIRCHE-II 评分。这是一项对 41 名接受 CNI 免费免疫抑制治疗且有可用肝移植活检的肝移植受者的回顾性研究。对供体和受者进行 HLA 分型。使用 PIRCHE-II 算法计算可以由受者 HLA-DRB1 分子呈递的 HLA 衍生错配肽表位。使用接收者操作特性曲线和随后的单变量和多变量分析评估 PIRCHE-II 评分与移植物免疫介导事件之间的关联。与具有正常肝移植物的患者相比,发生细胞性排斥反应、体液性排斥反应或严重门脉炎症的 CNI 免费患者的平均 PIRCHE-II 评分更高。PIRCHE-II 评分和供体年龄是 CNI 免费患者肝移植物存活的独立危险因素(HR:8.0,95%CI:1.3-49,p=0.02;和 HR:0.88,95%CI:0.00-0.96,p=0.007)。PIRCHE-II 评分可预测 CNI 免费患者肝移植后的肝移植物存活。需要更大的研究来证实这些结果。

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