PIRCHE AG, Berlin, Germany.
Center for Translational Immunology, University Medical Center, Utrecht, Netherlands.
Methods Mol Biol. 2024;2809:171-192. doi: 10.1007/978-1-0716-3874-3_12.
To optimize outcomes in solid organ transplantation, the HLA genes are regularly compared and matched between the donor and recipient. However, in many cases a transplant cannot be fully matched, due to widespread variation across populations and the hyperpolymorphism of HLA alleles. Mismatches of the HLA molecules in transplanted tissue can be recognized by immune cells of the recipient, leading to immune response and possibly organ rejection. These adverse outcomes are reduced by analysis using epitope-focused models that consider the immune relevance of the mismatched HLA.PIRCHE, an acronym for Predicted Indirectly ReCognizable HLA Epitopes, aims to categorize and quantify HLA mismatches in a patient-donor pair by predicting HLA-derived T cell epitopes. Specifically, the algorithm predicts and counts the HLA-derived peptides that can be presented by the host HLA, known as indirectly-presented T cell epitopes. Looking at the immune-relevant epitopes within HLA allows a more biologically relevant understanding of immune response, and provides an expanded donor pool for a more refined matching strategy compared with allele-level matching. This PIRCHE algorithm is available for analysis of single transplantations, as well as bulk analysis for population studies and statistical analysis for comparison of probability of organ availability and risk profiles.
为了优化实体器官移植的结果，供体和受者之间通常会对 HLA 基因进行比较和匹配。然而，由于人群中广泛的变异和 HLA 等位基因的高度多态性，许多情况下无法完全匹配移植。移植组织中 HLA 分子的不匹配可被受者的免疫细胞识别，导致免疫反应并可能导致器官排斥。通过使用考虑到不匹配 HLA 的免疫相关性的表位聚焦模型进行分析，可以减少这些不良结果。
PIRCHE 是“预测间接可识别 HLA 表位”的缩写，旨在通过预测 HLA 衍生的 T 细胞表位，对患者-供体对中的 HLA 不匹配进行分类和量化。具体来说，该算法预测并计算可以由宿主 HLA 呈递的 HLA 衍生肽，称为间接呈递的 T 细胞表位。研究 HLA 中的免疫相关表位可以更深入地了解免疫反应的生物学相关性，并提供更广泛的供体池，用于更精细的匹配策略，与等位基因水平匹配相比。这种 PIRCHE 算法可用于单一移植的分析，也可用于群体研究的批量分析和概率器官可用性和风险概况比较的统计分析。
