Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation

IF 2.2 4区 医学 Q3 HEMATOLOGY Best Practice & Research Clinical Haematology Pub Date : 2024-05-15 DOI:10.1016/j.beha.2024.101555
Kyra J. Fuchs, J.H. Frederik Falkenburg, Marieke Griffioen
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Abstract

Allogeneic hematopoietic cell transplantation (alloHCT) provides a potential curative treatment for haematological malignancies. The therapeutic Graft-versus-Leukaemia (GvL) effect is induced by donor T cells attacking patient hematopoietic (malignant) cells. However, if healthy non-hematopoietic tissues are targeted, Graft-versus-Disease (GvHD) may develop. After HLA-matched alloHCT, GvL and GvHD are induced by donor T cells recognizing polymorphic peptides presented by HLA on patient cells, so-called minor histocompatibility antigens (MiHAs). The balance between GvL and GvHD depends on the tissue distribution of MiHAs and T-cell frequencies targeting these MiHAs. T cells against broadly expressed MiHAs induce GvL and GvHD, whereas those targeting MiHAs with hematopoietic-restricted expression induce GvL without GvHD. Recently, the MiHA repertoire identified in natural immune responses after alloHCT was expanded to 159 total HLA-I-restricted MiHAs, including 14 hematopoietic-restricted MiHAs. This review explores their potential relevance to predict, monitor, and manipulate GvL and GvHD for improving clinical outcome after HLA-matched alloHCT.

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预测、监测或控制同种异体造血细胞移植后 GvL 和 GvHD 的主要组织相容性抗原
异基因造血细胞移植(alloHCT)是一种潜在的治疗血液恶性肿瘤的方法。治疗性移植物抗白血病(GvL)效应是由供体 T 细胞攻击患者造血(恶性)细胞引起的。但是,如果健康的非造血组织成为攻击目标,则可能出现移植物抗宿主疾病(GvHD)。在 HLA 相匹配的同种异体移植后,供体 T 细胞会识别患者细胞上由 HLA 呈现的多态肽,即所谓的次要组织相容性抗原(MiHA),从而诱发 GvL 和 GvHD。GvL和GvHD之间的平衡取决于MiHAs的组织分布和靶向这些MiHAs的T细胞频率。针对广泛表达的 MiHAs 的 T 细胞会诱发 GvL 和 GvHD,而针对造血受限表达的 MiHAs 的 T 细胞则会诱发 GvL 而不诱发 GvHD。最近,在同种异体移植后的天然免疫反应中发现的 MiHA 反应谱系扩展到了 159 种 HLA-I 限制性 MiHA,其中包括 14 种造血限制性 MiHA。本综述探讨了它们与预测、监测和控制 GvL 和 GvHD 的潜在相关性,以改善 HLA 匹配异体HCT 后的临床预后。
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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Best Practice & Research Clinical Haematology publishes review articles integrating the results from the latest original research articles into practical, evidence-based review articles. These articles seek to address the key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach which focuses on the key questions to be addressed, clearly defining what is known and not known, covering the spectrum of clinical and laboratory haematological practice and research. Although most reviews are invited, the Editor welcomes suggestions from potential authors.
期刊最新文献
Editorial Board From clones to immunopeptidomes: New developments in the characterization of permissive HLA-DP mismatches in hematopoietic cell transplantation Relevance of donor-specific HLA antibodies in hematopoietic cell transplantation HLA structure and function in hematopoietic-cell transplantation Special issue 37.3: “Genetics and function of HLA and immune-related genes in hematopoietic cell transplantation and cellular immunotherapy”
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