Quantifying HLA Mismatches at Epitope Level in Haplo-HSCT: Impact in the Outcome in Strategies Using PTCy

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA Pub Date : 2024-11-12 DOI:10.1111/tan.15738

Francisco Javier Gil-Etayo, Jairo Eduardo Niño-Ramírez, Marta Fonseca-Santos, Daniel Arroyo-Sánchez, Almudena Navarro-Bailón, Ariadna Vicente Parra, Isabel Jiménez Hernaz, Pilar Terradillos Sánchez, Francisco Boix, Miguel Alcoceba, Luis Marín, Estefanía Pérez-López, Mónica Cabrero, Ana África Martín-López, Miriam López, Mónica Baile, Alejandro Avendaño, Almudena Cabero, Ana García-Bacelar, Lourdes Vázquez, Fermín Sánchez-Guijo, Ramón García-Sanz, Lucía López-Corral, Amalia Tejeda Velarde

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Abstract

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is one of the most effective therapies for treating malignant haematological disorders. However, HLA disparities are significant barriers to the success of this process since they increase the risk of graft versus host disease (GvHD). HLA disparities quantification could help to anticipate the probability and degree of GvHD, but the best tool for such quantification remains a challenge. The aim of this study was to quantify the degree of HLA epitope incompatibilities using PIRCHE (Predicted Indirectly Recognisable HLA Epitopes) algorithm for immunogenicity prediction and their potential relationship with GvHD degree and clinical outcome. We studied 145 patients who underwent a haplo-HSCT with post-transplant cyclophosphamide (PTCy) from a related donor between 2013 and 2020 at our centre evaluating molecular HLA mismatches by PIRCHE-algorithm. Patients with PIRCHE Score (PS) I + II > 38 in GvH direction, developed acute GvHD grade II–IV earlier than their counterparts (HR: 1.71, 95% CI: 1.02–2.87, p = 0.032). In addition, PS-B > 1 in GvH direction was an independent risk factor for chronic GvHD, (HR: 2.51, 95% CI 1.17–5.36, p = 0.017). A higher incidence of relapse was found for patients with PS-II > 28 HvG (HR: 9.16, 95% CI: 2.47–33.92, p < 0.001) which also favoured a worse GvHD/relapse-free survival in patients with PS-II > 27 in HvG direction (HR: 1.88, 95% CI: 1.11–3.18, p = 0.017). These findings indicate that the alloreactivity inferred by epitope HLA disparities is associated with post-transplant outcomes. Thus, analysing PS could benefit the selection of the most suitable donors allowing patient stratification based on HLA mismatches in the context of haplo-HSCT with PTCy.

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在表位水平量化单倍体造血干细胞移植中的 HLA 错配：使用 PTCy 策略对结果的影响。

单倍体造血干细胞移植（haplo-HSCT）是治疗恶性血液病最有效的疗法之一。然而，HLA差异会增加移植物抗宿主疾病（GvHD）的风险，从而严重阻碍这一过程的成功。量化 HLA 差异有助于预测 GvHD 的概率和程度，但如何选择最佳工具进行量化仍是一项挑战。本研究的目的是使用用于免疫原性预测的 PIRCHE（Predicted Indirectly Recognisable HLA Epitopes）算法量化 HLA 表位不相容程度及其与 GvHD 程度和临床结果的潜在关系。我们研究了 2013 年至 2020 年期间在本中心接受单倍体造血干细胞移植并使用移植后环磷酰胺（PTCy）的 145 例患者，通过 PIRCHE 算法评估分子 HLA 错配情况。GvH方向上PIRCHE评分（PS）I + II > 38的患者比同类患者更早出现II-IV级急性GvHD（HR：1.71，95% CI：1.02-2.87，P = 0.032）。此外，GvH 方向的 PS-B > 1 是慢性 GvHD 的独立危险因素（HR：2.51，95% CI 1.17-5.36，p = 0.017）。PS-II > 28 HvG 的患者复发率更高（HR：9.16，95% CI：2.47-33.92，p 27，HvG 方向）（HR：1.88，95% CI：1.11-3.18，p = 0.017）。这些发现表明，由表位 HLA 差异推断出的异体反应与移植后的结果有关。因此，分析 PS 有利于选择最合适的供体，从而在使用 PTCy 进行单倍体造血干细胞移植时根据 HLA 错配情况对患者进行分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

HLA Immunology and Microbiology-Immunology

CiteScore

3.00

自引率

28.80%

发文量

368

期刊介绍： HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.