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肾移植中免疫遗传学及移植后事件的新进展

Novel Aspects of Immunogenetics and Post-Transplant Events in Kidney Transplantation.

作者信息

Helanterä Ilkka, Markkinen Salla, Partanen Jukka, Hyvärinen Kati

机构信息

Transplantation and Liver Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Finnish Red Cross Blood Service, Helsinki, Finland.

出版信息

Transpl Int. 2024 Dec 5;37:13317. doi: 10.3389/ti.2024.13317. eCollection 2024.

Abstract

HLA typing and matching have been crucial in kidney transplantation, but methods for assessing tissue histocompatibility have advanced significantly. While serological-level HLA typing remains common, it captures only a small fraction of true HLA variation, and molecular matching is already replacing traditional HLA matching. Recent studies have expanded our understanding of genetic tissue compatibility beyond HLA loci. Candidate gene analyses and genome-wide association studies (GWAS) have identified genetic factors linked to post-transplant complications, though replication of these findings is challenging. An alternative approach involves genome-wide matching of genes or genetic variations. This method has shown promise in hematopoietic stem cell and kidney transplantation. For instance, homozygous gene deletions in LIMS1 or complement factor H (CFH) genes have been associated with acute rejection risk. This may be due to alloimmune responses against proteins absent in the patient but present in the graft, or due to the missing protein's function. Genetic studies in clinical medicine face challenges due to the interplay of genetic and environmental factors, necessitating large datasets for meaningful associations. International collaboration and large consortia, like iGeneTRAin, are essential for validating findings and advancing the field. This review highlights recent advancements in immunogenetics and tissue histocompatibility, emphasizing future research directions.

摘要

HLA分型与匹配在肾移植中一直至关重要,但评估组织相容性的方法已经取得了显著进展。虽然血清学水平的HLA分型仍然很常见,但它只能捕捉到真正HLA变异的一小部分,分子匹配已经在取代传统的HLA匹配。最近的研究扩展了我们对基因组织相容性的理解,超出了HLA基因座的范围。候选基因分析和全基因组关联研究(GWAS)已经确定了与移植后并发症相关的遗传因素,尽管这些发现的重复验证具有挑战性。另一种方法涉及基因或遗传变异的全基因组匹配。这种方法在造血干细胞移植和肾移植中已显示出前景。例如,LIMS1或补体因子H(CFH)基因的纯合基因缺失与急性排斥风险相关。这可能是由于针对患者体内不存在但移植物中存在的蛋白质的同种免疫反应,或者是由于缺失蛋白质的功能。由于遗传和环境因素的相互作用,临床医学中的遗传学研究面临挑战,需要大型数据集才能得出有意义的关联。国际合作和大型联盟,如iGeneTRAin,对于验证研究结果和推动该领域发展至关重要。本综述重点介绍了免疫遗传学和组织相容性方面的最新进展,强调了未来的研究方向。

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