Transplant immunology最新文献_第6页

Pre-donation statin therapy to improve solid organ transplant outcomes 捐献前他汀类药物治疗改善实体器官移植结果

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-06 DOI: 10.1016/j.trim.2025.102283

Juhi R. Patel , John Dark , Daniel Harvey , Kulwant Dhadwal

Background

Inflammatory injury in organ donors, particularly after brain death and during ischemia-reperfusion, contributes to graft dysfunction, rejection, and reduced survival. Statins, beyond their lipid-lowering role, exert pleiotropic anti-inflammatory and immunomodulatory effects, including IL-6 suppression, NF-κB inhibition, immune cell modulation, and potential alteration of exosome secretion.

Methods

Building upon this background, this narrative review synthesises preclinical and clinical evidence on pre-donation statin therapy in solid organ transplantation. Specifically, we examine mechanistic pathways, such as cytokine signalling, vascular protection, and exosome modulation, alongside clinical data from heart, liver, lung, and kidney transplantation.

Results

In terms of outcomes, preclinical models consistently demonstrate reduced inflammatory burden, preserved microvascular integrity, and improved graft function with donor statin therapy. Moving to clinical studies, limited randomised controlled trials suggest early biochemical and haemodynamic benefits, such as reduced cardiac biomarkers, lower ALT in liver recipients, and reduced primary graft dysfunction in lung recipients. However, evidence for improved long-term graft survival, rejection rates, or mortality is inconsistent. Most trials are underpowered, single-centre, and lack mechanistic endpoint analysis, and data on donation after circulatory death and living donors remain sparse.

Conclusions

Pre-donation statin therapy is biologically plausible, safe in early studies, and supported by robust mechanistic rationale, yet definitive clinical benefit remains unproven. Large, multi-centre trials incorporating mechanistic and clinical endpoints, such as the ongoing SIGNET study, are essential to determine whether this strategy should be integrated into standard donor management.

背景：器官供体的炎症性损伤，特别是脑死亡后和缺血再灌注期间，会导致移植物功能障碍、排斥反应和生存率降低。他汀类药物除了具有降脂作用外，还具有多种抗炎和免疫调节作用，包括抑制IL-6、抑制NF-κB、调节免疫细胞和潜在改变外泌体分泌。方法基于此背景，本文综述了他汀类药物在实体器官移植中的临床前和临床证据。具体来说，我们研究了机制途径，如细胞因子信号传导、血管保护和外泌体调节，以及心脏、肝脏、肺和肾移植的临床数据。结果：临床前模型一致显示，他汀类药物治疗减轻了炎症负担，保持了微血管完整性，改善了移植物功能。转向临床研究，有限的随机对照试验表明早期生化和血流动力学益处，如心脏生物标志物降低，肝受体ALT降低，肺受体原发性移植物功能障碍减少。然而，改善移植的长期存活率、排异率或死亡率的证据并不一致。大多数试验缺乏动力，单中心，缺乏机制终点分析，并且关于循环死亡和活体供体后捐赠的数据仍然很少。结论捐献前他汀类药物治疗在生物学上是合理的，在早期研究中是安全的，并且有强大的机制理论支持，但明确的临床益处仍未得到证实。包括机制和临床终点的大型多中心试验，如正在进行的SIGNET研究，对于确定该策略是否应纳入标准供体管理至关重要。

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引用次数: 0

Pre-transplant compatibility testing: Transition from CDCXM to flow cytometry in India 移植前相容性测试：印度从CDCXM到流式细胞术的过渡。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-05 DOI: 10.1016/j.trim.2025.102281

Kashyap Shubham, Aseem K Tiwari, Chauhan Rajni, Mehra Simmi, Bhardwaj Gunjan, Rani Neha, Kahlon Simran

Over 60 % of kidney transplant candidates are non-sensitised while remaining 40 % are sensitised because of previous exposure to human alloantigens during previous transplants, blood transfusions, and pregnancy in women. Pre-transplant compatibility testing is mandatory prior to renal transplantation for detecting the presence of donor-specific antibodies (DSAs), which are associated with early hyperacute/acute and later chronic rejections. Initially, complement-dependent cytotoxicity crossmatch (CDCXM) was used as a traditional method for detecting preformed DSAs. However, its limited sensitivity fails to detect low-level antibodies, and all non-complement-binding antibodies lead to early graft rejection despite a negative CDC-XM result. Flow cytometry crossmatch (FCXM), introduced in 1983, addresses these limitations by offering superior sensitivity in detecting DSAs. FCXM uses indirect immunofluorescence to differentiate T cell (expressing class I HLA) and B cell (expressing class I/II HLAs) reactivities providing a more precise assessment of DSAs, significantly decreasing the risk of rejection. Studies demonstrate that positive FCXM results, even with negative CDC-XM, correlate with higher rejection rates and reduced graft survival. Various modifications, including pronase treatment and especially streamlined Halifax and Halifaster protocols, have improved the test's specificity and speed. Despite its advantages, FCXM is also susceptible to potential false-positive and false-negative results because of non-HLA antibodies, cross-reactivity with therapeutic agents, and other technical factors. Nonetheless, FCXM remains a gold standard in modern transplantation immunology, enhancing safety of graft outcomes through better identification of immunologically significant DSAs. This review outlines the transition from CDCXM to FCXM in the Indian context, emphasizing its impact on pre-transplant testing and clinical decision-making.

超过60% %的肾移植候选者不敏感，而剩余的40% %由于先前移植、输血和妇女怀孕期间接触过人类同种异体抗原而敏感。移植前相容性测试是强制性的，用于检测供体特异性抗体（dsa）的存在，这与早期超急性/急性和后来的慢性排斥反应有关。最初，补体依赖性细胞毒性交叉匹配（CDCXM）是检测预成型dsa的传统方法。然而，其有限的敏感性无法检测低水平抗体，并且尽管CDC-XM结果为阴性，但所有非补体结合抗体都会导致早期移植排斥反应。1983年引入的流式细胞仪交叉匹配（FCXM）通过在检测dsa方面提供卓越的灵敏度来解决这些限制。FCXM使用间接免疫荧光区分T细胞（表达I类HLA）和B细胞（表达I/II类HLA）的反应性，提供更精确的dsa评估，显著降低排斥反应的风险。研究表明，FCXM阳性结果，即使是CDC-XM阴性，也与更高的排异率和更低的移植物存活率相关。各种改进，包括pronase治疗，特别是简化的Halifax和Halifaster方案，提高了测试的特异性和速度。尽管FCXM具有优势，但由于非hla抗体、与治疗药物的交叉反应性和其他技术因素，FCXM也容易出现潜在的假阳性和假阴性结果。尽管如此，FCXM仍然是现代移植免疫学的金标准，通过更好地识别具有免疫学意义的dsa来提高移植结果的安全性。这篇综述概述了在印度从CDCXM到FCXM的转变，强调了其对移植前检测和临床决策的影响。

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引用次数: 0

Fxyd5 downregulation protects the heart from ischemia/reperfusion injury by suppressing myocardial inflammation Fxyd5下调通过抑制心肌炎症保护心脏免受缺血/再灌注损伤。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-03 DOI: 10.1016/j.trim.2025.102282

Lei Zhang , Junjie Xu , Fujiang Cui , Jin Jin , Liwen Liu , Lei Wang , Yuxia Gao

Background

Myocardial ischemia/reperfusion (I/R) injury is a common cause of death. FXYD domain-containing ion transport regulator-5 (Fxyd5) is a type I membrane protein that plays a significant role in mediating cellular functions. However, the expression and function of Fxyd5 in myocardial I/R injury remain unclear.

Methods

Male C57BL/6 mice (8–10 weeks) were subjected to myocardial I/R by ligating the left anterior descending coronary artery. Preventive intervention was performed using adeno-associated virus 9 (AAV9)-mediated Fxyd5 knockdown. An in vitro hypoxia/reoxygenation (H/R) in H9c2 cardiomyoblasts was used for validation.

Results

Myocardial I/R injury significantly upregulated Fxyd5 expression (p < 0.01). Silencing Fxyd5 markedly improved cardiac function, as evidenced by a 58.0 % increase in EF (p < 0.01) and a 54.5 % reduction in infarct size (p < 0.01). Fxyd5 knockdown also attenuated myocardial apoptosis and inflammation, demonstrated by decreased cleaved caspase-3 expression and reduced levels of IL-6 (−44.2 %) and TNF-α (−42.7 %) (p < 0.01). Mechanistically, Fxyd5 silencing suppressed NF-κB activation, and these protective effects were confirmed in vitro in H/R-treated cardiomyocytes.

Conclusion

Fxyd5 silencing significantly attenuated I/R-induced myocardial injury, reduced infarct size, and improved cardiac function, while also decreasing apoptosis and inflammatory cytokine expression (p < 0.01). These findings indicate that Fxyd5 contributes to the pathogenesis of myocardial I/R injury and that its inhibition confers cardioprotective effects, partly through suppression of the NF-κB pathway.

背景：心肌缺血/再灌注（I/R）损伤是常见的死亡原因。FXYD结构域离子运输调节因子-5 （Fxyd5）是一种I型膜蛋白，在调节细胞功能中起重要作用。然而，Fxyd5在心肌I/R损伤中的表达和功能尚不清楚。方法：雄性C57BL/6小鼠（8 ~ 10 周）结扎左冠状动脉前降支进行心肌I/R。采用腺相关病毒9 （AAV9）介导的Fxyd5敲低进行预防性干预。采用体外缺氧/再氧化（H/R）法对H9c2型心肌细胞进行验证。结果：心肌I/R损伤可显著上调Fxyd5的表达（p ）结论：Fxyd5沉默可显著减轻I/R诱导的心肌损伤，减少梗死面积，改善心功能，同时减少细胞凋亡和炎症细胞因子的表达(p

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引用次数: 0

IL-6 amplifies corneal transplant alloimmunity by inducing dysfunctional IFN-γ- secreting Treg through the VEGFA-VEGFR1 axis IL-6通过VEGFA-VEGFR1轴诱导功能失调的IFN-γ分泌Treg，从而增强角膜移植异体免疫

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-02 DOI: 10.1016/j.trim.2025.102284

Seokjoo Lee, Akitomo Narimatsu, Neda Heydarian, Mark Krauthammer, Shilpy Bhullar, Yihe Chen, Sunil K. Chauhan, Thomas H. Dohlman, Reza Dana

Background

Corneal allografts generally exhibit high acceptance due to the immune-privileged ocular microenvironment. Regulatory T cells (Treg) promote graft tolerance; however, in a vascularized milieu, they may acquire a pro-inflammatory phenotype. We investigated how dysfunctional Treg contribute to graft rejection through the VEGFA–VEGFR1 axis.

Methods

Treg were treated with IL-6 and VEGFA, and their phenotype—including FoxP3, IL-10, and IFN-γ—was evaluated with or without a VEGFR1 antagonist (αVEGFR1) using PCR, immunoblotting, ELISA, and flow cytometry. Suppressive function was assessed by T-cell proliferation assays, corneal cell death by Annexin V staining, and graft survival by adoptive transfer of dysfunctional Treg into a transplantation model.

Results

IL-6 reduced FoxP3 (p < 0.0001) and upregulated VEGFR1 (p < 0.001). IL-6 plus VEGFA further decreased FoxP3 (p < 0.0001) and IL-10 (p < 0.0001) while increasing IFN-γ (p < 0.0001). αVEGFR1 reversed these effects, restoring FoxP3 (p < 0.0001) and IL-10 (p < 0.05) while reducing IFN-γ (p < 0.001). Functionally, IL-6/VEGFA-pretreated Treg showed impaired suppression of effector T-cell proliferation (p < 0.0001), an effect partially rescued by αVEGFR1 (p < 0.001). In ex vivo assays, fresh Treg prevented, whereas dysfunctional IFN-γ–secreting Treg induced, corneal cell death (p < 0.0001). In vivo, grafts injected with dysfunctional Treg were rejected within 3–7 weeks, while those with αVEGFR1-treated Treg showed improved survival and reduced cell death (p < 0.0001).

Conclusion

IL-6 impairs Treg via VEGFR1 upregulation, driving IFN-γ secretion through the VEGFA–VEGFR1 axis and promoting corneal cell death and graft rejection.

背景：由于免疫优越的眼微环境，同种异体角膜移植通常表现出较高的接受度。调节性T细胞（Treg）促进移植物耐受；然而，在血管化的环境中，它们可能获得促炎表型。我们研究了功能失调的Treg如何通过vegf - vegfr1轴促进移植排斥。方法分别用IL-6和VEGFA处理streg，采用PCR、免疫印迹、ELISA和流式细胞术检测在加或不加VEGFR1拮抗剂（αVEGFR1）的情况下FoxP3、IL-10和IFN-γ的表型。通过t细胞增殖试验评估抑制功能，通过膜联蛋白V染色评估角膜细胞死亡，通过将功能失调的Treg过继转移到移植模型中评估移植物存活。结果sil -6降低FoxP3 (p < 0.0001)，上调VEGFR1 （p < 0.001）。IL-6加VEGFA进一步降低FoxP3 （p < 0.0001）和IL-10 (p < 0.0001)，同时增加IFN-γ (p < 0.0001)。αVEGFR1逆转了这些影响，恢复FoxP3 （p < 0.0001）和IL-10 (p < 0.05)，同时降低IFN-γ (p < 0.001)。在功能上，IL-6/ vegfa预处理的Treg显示出对效应t细胞增殖的抑制受损（p < 0.0001）， αVEGFR1部分恢复了这一作用（p < 0.001）。在离体实验中，新鲜Treg可预防角膜细胞死亡，而功能失调的IFN-γ分泌Treg则可诱导角膜细胞死亡（p < 0.0001）。在体内，注射功能失调Treg的移植物在3-7周内出现排斥反应，而注射α vegfr1处理的Treg的移植物存活率提高，细胞死亡减少（p < 0.0001）。结论il -6通过VEGFR1上调Treg，通过VEGFA-VEGFR1轴驱动IFN-γ分泌，促进角膜细胞死亡和移植排斥反应。

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引用次数: 0

Myth or reality: Graft versus host disease after autologous hematopoietic cell transplantation, a multicentre experience 神话或现实：自体造血细胞移植后的移植物抗宿主病，一个多中心的经验。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-02 DOI: 10.1016/j.trim.2025.102286

Süreyya Yiğit Kaya , Leylagül Kaynar , Yaşa Gül Mutlu , Mihriban Yıldırım , İstemi Serin , Duygu Nurdan Avcı , Gülşah Akyol , Osman Şahin , Senem Maral , Ömür Gökmen Sevindik

Acute graft-versus-host disease (aGvHD) is a rare but clinically significant complication of autologous hematopoietic cell transplantation. The aim of this retrospective multicenter study was to evaluate the clinical features, outcomes and risk factors associated with autologous graft-versus-host disease (auto-GvHD) in 19 patients. The cohort included 12 multiple myeloma and 7 lymphoma patients with a median age of 58 years. All patients developed aGvHD, predominantly involving the gastrointestinal tract, skin or liver, with isolated organ involvement in the majority. Conditioning regimens commonly included melphalan and all patients underwent peripheral blood hematopoietic cell transplantation. First-line treatment with topical corticosteroids and systemic methylprednisolone was effective in most cases, while steroid-resistant GvHD was successfully treated with cyclosporine and ruxolitinib. Lenalidomide maintenance therapy in multiple myeloma patients did not lead to GvHD recurrence. No GvHD-related mortality was observed and complete responses were achieved in all treated cases. These findings underscore the importance of early detection and prompt treatment of auto-GvHD, particularly in high-risk populations and highlight the need for further research to elucidate its pathophysiology and optimise management strategies.

急性移植物抗宿主病（aGvHD）是一种罕见但临床上重要的自体造血细胞移植并发症。本回顾性多中心研究的目的是评估19例自体移植物抗宿主病（auto-GvHD）患者的临床特征、结局和相关危险因素。该队列包括12例多发性骨髓瘤和7例淋巴瘤患者，中位年龄为58 岁。所有患者均发展为aGvHD，主要累及胃肠道、皮肤或肝脏，多数累及孤立器官。调理方案通常包括美法仑，所有患者均行外周血造血细胞移植。在大多数病例中，使用局部皮质类固醇和全身甲基强的松龙进行一线治疗是有效的，而使用环孢素和鲁索利替尼成功治疗了类固醇抵抗性GvHD。多发性骨髓瘤患者来那度胺维持治疗未导致GvHD复发。未观察到与gvhd相关的死亡率，所有治疗病例均达到完全缓解。这些发现强调了早期发现和及时治疗自身gvhd的重要性，特别是在高危人群中，并强调了进一步研究阐明其病理生理和优化管理策略的必要性。

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引用次数: 0

Case report: Hyperacute rejection of living relative kidney transplantation caused by colony-stimulating factor 2 antibodies 集落刺激因子2抗体致活体亲属肾移植超急性排斥反应一例报告。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-02 DOI: 10.1016/j.trim.2025.102285

Qixuan Li , Zhaoying Pang , Meng Yang , Lunli Xiang , Xulian Hu , Qin Yang , Hongwen Zhao , Jie Li , Xiaosong Xu

Background

Kidney transplantation (KT) stands as a highly effective, life-saving intervention for patients with end-stage renal disease, offering substantial improvements in both quality of life and long-term survival. However, one of the most critical challenges that can arise in this procedure is hyperacute rejection (HR). This severe immune response occurs almost immediately after transplantation and can place the patient at a heightened risk of serious complications and even drastically jeopardizes the survival of the transplanted kidney. This study reports a case of HR mediated by colony-stimulating factor 2 (CSF2) antibodies following living-related KT, elaborates on its clinical features, diagnostic workflow, and therapeutic management, and analyzes the role of CSF2 antibodies in KT-related immunity. The findings aim to provide clinical reference for optimizing HR prevention and management in KT practice.

背景：肾移植（KT）是一种非常有效的、挽救终末期肾病患者生命的干预措施，在生活质量和长期生存方面都有实质性的改善。然而，在这个过程中可能出现的最关键的挑战之一是超急性排斥反应（HR）。这种严重的免疫反应几乎在移植后立即发生，并可能使患者面临严重并发症的高风险，甚至严重危及移植肾脏的存活。本研究报道一例集落刺激因子2 （colony stimulating factor 2, CSF2）抗体介导的活相关性KT HR，阐述其临床特点、诊断流程和治疗管理，分析CSF2抗体在KT相关免疫中的作用。研究结果旨在为优化KT实践中的人力资源预防和管理提供临床参考。

引用次数: 0

Lung transplantation in patients with diabetes: A systematic review 糖尿病患者的肺移植：一项系统综述。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-02 DOI: 10.1016/j.trim.2025.102279

Fatemeh Moosaie , Shiva Abedinzadeh , Sepide Javankiani , Fatemeh Asli , Prajjwol Luitel , Seyede Marzie Fatemi Abhari

Background and aim

Lung transplantation (LTx) is increasingly performed worldwide, yet post-transplant survival remains lower than for other solid organs. Diabetes mellitus (DM) is common among LTx recipients and impacts outcomes. This systematic review evaluates the effects of DM on LTx outcomes and the influence of diabetes onset timing on survival.

Methods

A systematic search was conducted in December 2024 across PubMed, Scopus, and Web of Science to identify original studies or case series involving patients with pre-transplant DM undergoing or waitlisted for LTx. The quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS).

Results

Eighty-four studies published between 1992 and 2024 were included, with sample sizes ranging from 10 to over 4 million patients and follow-up from 1 to 25 years. Diabetes was present in 8–56 % of lung transplant recipients. Patients with diabetes, including pre-existing diabetes, cystic fibrosis-related diabetes (CFRD), and new-onset diabetes after transplantation (NODAT), showed higher risks of infections, acute kidney injury, thromboembolic events, chronic lung allograft dysfunction, and cardiovascular complications. Diabetes was consistently associated with increased short- and long-term mortality, prolonged mechanical ventilation, and greater hospitalization rates.

Conclusion

Diabetes—whether present before or developing after lung transplantation—is a significant predictor of adverse clinical outcomes and mortality. These findings underscore the need for careful perioperative glycemic management, tailored immunosuppression, and vigilant monitoring to reduce complications. Further standardized, prospective research is essential to guide optimal diabetes management and improve survival in lung transplant recipients.

背景和目的：肺移植（LTx）越来越多地在世界范围内进行，但移植后生存率仍然低于其他实体器官。糖尿病（DM）在LTx接受者中很常见，并影响预后。本系统综述评估了糖尿病对LTx结局的影响以及糖尿病发病时间对生存的影响。方法：于2024年12月对PubMed、Scopus和Web of Science进行系统检索，以确定涉及移植前糖尿病患者接受或等待LTx的原始研究或病例系列。纳入研究的质量采用非随机研究方法学指数（Methodological Index for non - random studies，未成年人）进行评估。结果：纳入了1992年至2024年间发表的84项研究，样本量从10万到400多万患者不等，随访时间为1至25 年。8- 56%的肺移植受者存在糖尿病 %。糖尿病患者，包括既往糖尿病、囊性纤维化相关糖尿病（CFRD）和移植后新发糖尿病（NODAT），感染、急性肾损伤、血栓栓塞事件、慢性同种异体肺功能障碍和心血管并发症的风险更高。糖尿病始终与增加的短期和长期死亡率、延长的机械通气时间和更高的住院率相关。结论：糖尿病——无论是在肺移植前出现还是在肺移植后发生——是不良临床结果和死亡率的重要预测因子。这些发现强调了围手术期谨慎的血糖管理、量身定制的免疫抑制和警惕监测以减少并发症的必要性。进一步标准化的前瞻性研究对于指导最佳糖尿病管理和提高肺移植受者的生存率至关重要。

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引用次数: 0

Exploration of causal relationship between transplant rejection and immune cells: A two-sample Mendelian randomization study 移植排斥反应与免疫细胞间因果关系的探索：一项双样本孟德尔随机化研究

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-08-24 DOI: 10.1016/j.trim.2025.102278

Fei Xue , Xuanpeng Wu , Ming Ni , Tao Jiang , Hao Wang , Yunfeng Ma , Qifei Wu

Post-transplant rejection is a serious problem for patients undergoing organ transplantation. It is currently believed that immune-related factors are the main causes of transplant rejection, but the roles of many immune cell phenotypes are still unclear.

We utilized Mendelian randomization analysis to explore the association between 731 immune cell and the risk of transplant rejection.

We systematically analyzed 731 immune cell phenotypes (including absolute counts, surface markers, and functional states) from peripheral blood of 3657 European individuals. Genetic instruments were selected at a genome-wide significance threshold (p < 1 × 10⁻⁵) to assess bidirectional causal relationships with transplant rejection events from FinnGen biobank (n = 16,380,395 SNPs). Forward MR analysis identified 33 immune phenotypes significantly associated with rejection risk: 19 protective (odds ratio [OR] < 1, p < 0.05) predominantly in B cell subsets, and 14 risk-enhancing phenotypes (OR > 1). Reverse MR revealed that rejection events causally altered 34 immune phenotypes, upregulated 18 effector phenotypes and downregulated 16 regulatory phenotypes. Sensitivity analyses confirmed robustness against pleiotropy (MR-Egger intercept p > 0.05, MR-PRESSO global test p > 0.01 and heterogeneity test p > 0.05). These findings highlight the dynamic interplay between B cell plasticity and Treg depletion in transplant outcomes, suggesting novel therapeutic targets for rejection prevention.

Our research confirms the close relationship between transplant rejection and immune cells, especially that certain B cell subsets are causally linked to a lower risk of transplant rejection, providing new targets and insights for future clinical treatments.

移植后排斥反应是器官移植患者面临的一个严重问题。目前认为免疫相关因素是移植排斥反应的主要原因，但许多免疫细胞表型的作用尚不清楚。我们使用孟德尔随机化分析来探讨731免疫细胞与移植排斥风险之间的关系。我们系统地分析了3657名欧洲人外周血中的731种免疫细胞表型（包括绝对计数、表面标记物和功能状态）。在全基因组显著性阈值（p < 1 × 10−5）下选择遗传工具来评估与FinnGen生物银行移植排斥事件的双向因果关系（n = 16,380,395个snp）。前瞻性磁共振分析确定了33种与排斥风险显著相关的免疫表型：19种保护性表型（优势比[OR] <； 1, p < 0.05），主要发生在B细胞亚群中，14种风险增强表型（OR > 1）。反向MR显示，排斥事件导致34种免疫表型改变，18种效应表型上调，16种调节性表型下调。敏感性分析证实了对多效性的稳健性（MR-Egger截距p >； 0.05， MR-PRESSO全局检验p >； 0.01，异质性检验p >； 0.05）。这些发现强调了B细胞可塑性和Treg耗竭在移植结果中的动态相互作用，提出了预防排斥反应的新治疗靶点。我们的研究证实了移植排斥反应与免疫细胞之间的密切关系，特别是某些B细胞亚群与移植排斥反应风险较低有因果关系，为未来的临床治疗提供了新的靶点和见解。

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引用次数: 0

Impacts of donor-specific anti-HLA antibodies on post-transplant clinical outcomes in hematopoietic stem cell transplantation: A systematic review and meta-analysis 供体特异性hla抗体对造血干细胞移植后临床结果的影响：一项系统综述和荟萃分析。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-08-07 DOI: 10.1016/j.trim.2025.102275

Muchen Liu , Zhongyu Kang , Huan Zhang

Background

Donor-specific antibodies (DSAs) are a major risk factor for adverse clinical outcomes in hematopoietic stem cell transplantation (HSCT). However, their clinical relevance remains controversial and unclear. This meta-analysis evaluated the impact of DSAs in HSCT.

Methods

This systematic review and meta-analysis compared outcomes between patients positive and negative for DSAs. Databases including PubMed, Embase, and Cochrane Library were searched for English-language studies published up to January 2025. Studies assessing DSAs and outcomes, including overall survival (OS), graft failure, poor graft function (PGF), poor engraftment rates, and graft-versus-host disease (GVHD). Pooled odds ratios and confidence intervals were calculated using fixed- or random-effects models.

Results

Thirty-two studies with 5555 patients with HSCT (557 DSA-positive, 4998 DSA-negative) were included. DSA positivity was considerably associated with increased risk of PGF, graft failure, and overall mortality. Additionally, patients with DSA-positive had lower OS. However, no notable associations were found with GVHD, neutrophil or platelet engraftment, relapse, or infections such as cytomegalovirus or Epstein-Barr virus. Study heterogeneity was moderate to high for several outcomes, necessitating the use of random-effects models.

Conclusion

DSAs are linked to poorer HSCT outcomes, particularly graft failure and reduced overall survival. Routine DSA screening and targeted interventions may improve outcomes.

背景：供体特异性抗体（dsa）是造血干细胞移植（HSCT）不良临床结果的主要危险因素。然而，它们的临床相关性仍然存在争议和不清楚。本荟萃分析评估了dsa在HSCT中的影响。方法：本系统综述和荟萃分析比较了dsa阳性和阴性患者的结果。检索了PubMed、Embase和Cochrane Library等数据库，检索了截至2025年1月发表的英语研究。评估dsa和结果的研究，包括总生存期（OS）、移植物衰竭、移植物功能不良（PGF）、移植物不良植入率和移植物抗宿主病（GVHD）。合并优势比和置信区间采用固定或随机效应模型计算。结果：32项研究纳入了5555例HSCT患者（557例dsa阳性，4998例dsa阴性）。DSA阳性与PGF、移植物衰竭和总死亡率增加的风险显著相关。此外，dsa阳性患者的OS较低。然而，与GVHD、中性粒细胞或血小板植入、复发或感染（如巨细胞病毒或eb病毒）没有明显的关联。有几个结果的研究异质性为中等到高度，因此需要使用随机效应模型。结论：dsa与较差的HSCT结果有关，特别是移植物失败和总生存率降低。常规DSA筛查和有针对性的干预可能改善预后。

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引用次数: 0

Research progress and current status of gene-edited-pig to non-human primate kidney xenotransplantation drug application 基因编辑猪对非人灵长类动物肾脏异种移植药物应用的研究进展及现状。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-08-07 DOI: 10.1016/j.trim.2025.102276

Shujun Yang , Hao Wei , Haihong Yang , Xilong Lin , Panfeng Shang , Shengkun Sun

Kidney transplantation is the only effective treatment for patients with end-stage renal disease (ESRD). With the application of gene-editing technology and modern immunosuppressants, kidney transplants from pigs with up to 12 edited genes have shown significant survival in non-human primates (NHP) and have been transplanted in handful of patients. Our review describes the most current progress in gene-edited pigs used for kidney xenotransplantation (KXTx) to NHP. Furthermore, this review reports about drug treatment options such as immune induction, immune maintenance, anti-inflammatory therapy, and anticoagulant therapy aiming to provide in prospects of KXTx. We stress the following highlights: 1) The application of induction and maintenance therapies with gene edited pigs for NHP KXTx; 2) The application of CD40-CD154 co-stimulatory pathway blockers as essential in immune maintenance medication; 3) The role of cytokines in monitoring of anti-inflammatory treatment’ and 4) The salvage administration measures during suspected rejection reactions can to some extent prolong the functional survival of the recipient kidney.

肾移植是终末期肾病（ESRD）患者唯一有效的治疗方法。随着基因编辑技术和现代免疫抑制剂的应用，带有多达12个编辑基因的猪肾移植在非人灵长类动物（NHP）中显示出显着的存活率，并已移植到少数患者身上。我们的综述描述了用于肾异种移植（KXTx）到NHP的基因编辑猪的最新进展。此外，本文综述了药物治疗方案，如免疫诱导、免疫维持、抗炎治疗和抗凝治疗，旨在为KXTx的前景提供参考。我们强调以下重点：1)NHP KXTx基因编辑猪诱导和维持疗法的应用；2) CD40-CD154共刺激途径阻断剂在免疫维持药物中的应用；3)细胞因子在抗炎治疗中的监测作用；4)在疑似排斥反应时采取补救性给药措施，可在一定程度上延长受体肾脏的功能生存期。

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