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计算方法在实体器官移植中促进基于表位的 HLA 匹配。

Computational Approaches to Facilitate Epitope-Based HLA Matching in Solid Organ Transplantation.

机构信息

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.

PIRCHE AG, Berlin, Germany.

出版信息

J Immunol Res. 2017;2017:9130879. doi: 10.1155/2017/9130879. Epub 2017 Feb 12.

Abstract

Epitope-based HLA matching has been emerged over the last few years as an improved method for HLA matching in solid organ transplantation. The epitope-based matching concept has been incorporated in both the PIRCHE-II and the HLAMatchmaker algorithm to find the most suitable donor for a recipient. For these algorithms, high-resolution HLA genotype data of both donor and recipient is required. Since high-resolution HLA genotype data is often not available, we developed a computational method which allows epitope-based HLA matching from serological split level HLA typing relying on HLA haplotype frequencies. To validate this method, we simulated a donor-recipient population for which PIRCHE-II and eplet values were calculated when using both high-resolution HLA genotype data and serological split level HLA typing. The majority of the serological split level HLA-determined / values did not or only slightly deviate from the reference group of high-resolution HLA-determined / values. This deviation was slightly increased when HLA-C or HLA-DQ was omitted from the input and was substantially decreased when using two-field resolution HLA genotype data of the recipient and serological split level HLA typing of the donor. Thus, our data suggest that our computational approach is a powerful tool to estimate PIRCHE-II/eplet values when high-resolution HLA genotype data is not available.

摘要

基于表位的 HLA 配型在过去几年中作为一种改进的实体器官移植中 HLA 配型的方法而出现。基于表位的匹配概念已被纳入 PIRCHE-II 和 HLAMatchmaker 算法中,以找到最适合受者的供者。对于这些算法,需要供者和受者的高分辨率 HLA 基因型数据。由于高分辨率 HLA 基因型数据通常不可用,我们开发了一种计算方法,该方法允许基于血清学分割水平 HLA 分型的表位 HLA 匹配,依赖于 HLA 单倍型频率。为了验证该方法,我们模拟了一个供受者群体,当使用高分辨率 HLA 基因型数据和血清学分割水平 HLA 分型时,计算了 PIRCHE-II 和 eplet 值。大多数血清学分割水平 HLA 确定的 / 值与高分辨率 HLA 确定的 / 值参考组没有或只有轻微偏差。当从输入中省略 HLA-C 或 HLA-DQ 时,这种偏差略有增加,而当使用受者的两域分辨率 HLA 基因型数据和供者的血清学分割水平 HLA 分型时,这种偏差则大大降低。因此,我们的数据表明,当无法获得高分辨率 HLA 基因型数据时,我们的计算方法是估计 PIRCHE-II/eplet 值的有力工具。

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