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HLA-C 基因座中抗体验证表位的数量是肝移植后 T 细胞介导排斥反应的独立因素。

Number of Antibody-verified Eplet in HLA-C Locus as an Independent Factor of T-cell-Mediated Rejection After Liver Transplantation.

机构信息

Immunology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.

Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital-IDIVAL, Santander, Spain.

出版信息

Transplantation. 2020 Mar;104(3):562-567. doi: 10.1097/TP.0000000000002921.

DOI:10.1097/TP.0000000000002921
PMID:31403556
Abstract

BACKGROUND

HLA mismatching is a risk factor for graft rejection in solid organ transplantation. Its definition is being rethought with the introduction of the eplets in organ allocation. The eplets are highly polymorphic regions of the HLA molecule that help to explain cross-reactivity of HLA antigens. The effect of eplet mismatch is well documented in renal and lung transplantation but there is no clear evidence in liver transplantation.

METHODS

Forty-three consecutive liver-graft donor/recipient pairs performed at our center from 2016 to 2018 were HLA typed. The quantification of antibody-verified eplets (VerEp) mismatch was performed with HLA-matchmaker 2.1 version.

RESULTS

A total of 9 patients suffered an episode of T-cell-mediated rejection (TCMR). No significant differences were observed in the number of A, B, DRB, DQA, and DQB VerEp. However, the mean of mismatches VerEp in locus C (VerEpC) was significantly increased in patients with acute rejection: 3.89 (1.36) versus 2.32 (1.82), P = 0.021. A total of 22 patients with high load of VerEpC (>2) had an increased risk of TCMR (P = 0.008). The time of TCMR-free after liver transplant was statistically reduced in high-load VerEpC group (log-rank test P = 0.019). Multivariate analysis demonstrated that high load of VerEpC was independently associated with TCMR (P = 0.038).

CONCLUSIONS

Patients with no or 1 eplet mismatch at the C locus are less likely to suffer TCMR after liver transplantation.

摘要

背景

HLA 错配是实体器官移植中移植物排斥的一个风险因素。随着器官分配中 eplets 的引入,其定义正在被重新思考。eplets 是 HLA 分子高度多态性的区域,有助于解释 HLA 抗原的交叉反应性。eplet 错配的影响在肾和肺移植中得到了很好的证明,但在肝移植中没有明确的证据。

方法

我们中心于 2016 年至 2018 年连续进行了 43 例肝移植供体/受者配对 HLA 分型。使用 HLA-matchmaker 2.1 版本对抗体验证的 eplets(VerEp)错配进行定量。

结果

共有 9 例患者发生 T 细胞介导的排斥反应(TCMR)。A、B、DRB、DQA 和 DQB VerEp 的错配数量无显著差异。然而,急性排斥反应患者的 VerEpC (VerEpC) 错配平均值显著增加:3.89(1.36)比 2.32(1.82),P = 0.021。VerEpC (VerEpC) 高负荷(>2)的 22 例患者发生 TCMR 的风险增加(P = 0.008)。高负荷 VerEpC 组肝移植后 TCMR 无时间明显缩短(对数秩检验 P = 0.019)。多变量分析表明,VerEpC 高负荷与 TCMR 独立相关(P = 0.038)。

结论

肝移植后,C 位点无错配或 1 个错配的患者发生 TCMR 的可能性较小。

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