Transplant immunology最新文献_第6页

Association between interleukin 6, C-reactive protein, and kidney transplantation outcomes: A systematic review and meta-analysis 白细胞介素6、c反应蛋白与肾移植结果之间的关系：一项系统综述和荟萃分析。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-10-04 DOI: 10.1016/j.trim.2025.102308

Lasin Ozbek , Berk Mizrak , Zeynep Y. Yilmaz , Mustafa Guldan , Derya G. Fidan , Sama Mahmoud Abdel-Rahman , Mehmet Kanbay

Background

Kidney transplant recipients experience heightened systemic inflammation, and biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and high-sensitivity CRP (hsCRP) have been proposed as prognostic indicators.

Objective

This meta-analysis evaluates the associations between IL-6, CRP, and hsCRP levels and all-cause mortality, cardiovascular events, and graft dysfunction in kidney transplant recipients.

Methods

A comprehensive search of PubMed, Web of Science, Scopus, Ovid MEDLINE, and the Cochrane Library until October 11, 2024, identified eligible studies reporting associations between IL-6, CRP, or hsCRP and clinical outcomes in adult kidney transplant recipients.

Results

The systematic review included 40 studies, with 18 meeting criteria for meta-analysis. Elevated IL-6 was associated with a higher risk of graft dysfunction (HR 1.53, 95 % CI 1.28–1.83; I² = 0 %) and all-cause mortality (HR 1.66, 95 % CI 1.05–2.61; I² = 97.2 %), but not cardiovascular events. CRP was associated with all-cause mortality (HR 2.07, 95 % CI 1.59–2.70; I² = 0 %) and cardiovascular events (HR 6.89, 95 % CI 2.52–18.85; I² = 0 %), but not cardiovascular mortality or graft dysfunction. Elevated hsCRP was associated with all-cause mortality (HR 1.29, 95 % CI 1.15–1.44; I² = 61 %), but not with cardiovascular events or graft dysfunction.

Conclusions

Among kidney transplant recipients, elevated levels of IL-6, CRP, and hsCRP were significantly associated with increased all-cause mortality, though the association of IL-6 with all-cause mortality showed substantial heterogeneity and should be interpreted with caution. IL-6 also emerged as a predictor of graft dysfunction, while CRP demonstrated a strong association with cardiovascular events. These findings highlight the potential role of inflammatory biomarkers, particularly IL-6 and CRP, in post-transplant risk stratification; however, further studies are needed to establish causality and clarify their clinical utility.

背景：肾移植受者会经历更高的全身性炎症，生物标志物如白细胞介素-6 （IL-6）、c反应蛋白（CRP）和高敏CRP （hsCRP）已被提出作为预后指标。目的：本荟萃分析评估IL-6、CRP和hsCRP水平与肾移植受者全因死亡率、心血管事件和移植物功能障碍之间的关系。方法：全面检索PubMed、Web of Science、Scopus、Ovid MEDLINE和Cochrane图书馆，直到2024年10月11日，确定了IL-6、CRP或hsCRP与成人肾移植受者临床结果相关的符合条件的研究。结果：系统评价纳入40项研究，其中18项符合meta分析标准。IL-6升高与移植物功能障碍的高风险（HR 1.53, 95 % CI 1.28-1.83; I2 = 0 %）和全因死亡率（HR 1.66, 95 % CI 1.05-2.61; I2 = 97.2 %）相关，但与心血管事件无关。CRP与全因死亡率（HR 2.07, 95 % CI 1.59-2.70; I2 = 0 %）和心血管事件（HR 6.89, 95 % CI 2.52-18.85; I2 = 0 %）相关，但与心血管死亡率或移植物功能障碍无关。hsCRP升高与全因死亡率相关（HR 1.29, 95 % CI 1.15-1.44; I2 = 61 %），但与心血管事件或移植物功能障碍无关。结论：在肾移植受者中，IL-6、CRP和hsCRP水平的升高与全因死亡率的增加显著相关，尽管IL-6与全因死亡率的关系显示出很大的异质性，应谨慎解释。IL-6也可作为移植物功能障碍的预测因子，而CRP则与心血管事件密切相关。这些发现强调了炎症生物标志物，特别是IL-6和CRP在移植后风险分层中的潜在作用；然而，需要进一步的研究来确定因果关系并阐明其临床应用。

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引用次数: 0

Prevalence and determinants of frailty–sarcopenia comorbidity in hospitalized patients undergoing liver transplantation for hepatic echinococcosis 因肝包虫病接受肝移植的住院患者虚弱-肌肉减少合并症的患病率和决定因素。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-11-11 DOI: 10.1016/j.trim.2025.102327

Sujun Wang , Huanhuan Wei , Yiliyaer Aihemaiti , Lijun Ma , Ying Tong , Fang Li

Objective

The aim of this study was to examine the prevalence and influencing factors of comorbid frailty and sarcopenia in hospitalized patients with hepatic echinococcosis undergoing liver transplantation, thereby providing evidence for targeted clinical interventions.

Methods

A convenience sampling method was used to recruit 118 patients who underwent liver transplantation and were hospitalized in the hepatobiliary echinococcosis departments of two tertiary grade A hospitals in Urumqi from March 2023 to July 2025. Data were collected using a general information questionnaire, the Liver Frailty Index (LFI), a sarcopenia screening questionnaire, the Social Support Rating Scale (SSRS), and a general health status scale. Univariate analyses were performed using analysis of variance (ANOVA), χ² tests, or non-parametric tests, as appropriate. Logistic regression analysis was conducted to identify factors associated with preoperative comorbidity of frailty and sarcopenia in liver transplant recipients.

Results

Valid data were obtained from 114 patients. The prevalence of comorbid frailty and sarcopenia in this patient population was 25.44 %. Logistic regression analysis indicated that older age, a higher number of comorbid chronic diseases, lower hemoglobin levels, and reduced social support were independent determinants (p < 0.05).

Conclusions

Comorbid frailty and sarcopenia were relatively prevalent among hospitalized patients with hepatic echinococcosis undergoing liver transplantation. Comprehensive preoperative evaluations should be conducted to identify these comorbidities, and targeted intervention strategies should be implemented promptly based on the identified determinants to mitigate disease progression.

目的：探讨肝包虫病住院肝移植患者伴发虚弱和肌肉减少症的患病率及影响因素，为有针对性的临床干预提供依据。方法：采用方便抽样的方法，选取乌鲁木齐市两家三级甲等医院肝胆包虫病科于2023年3月至2025年7月住院的肝移植患者118例。数据收集采用一般信息问卷、肝衰竭指数（LFI）、肌肉减少症筛查问卷、社会支持评定量表（SSRS）和一般健康状况量表。采用方差分析（ANOVA）、χ2检验或适当的非参数检验进行单因素分析。进行Logistic回归分析，以确定肝移植受者术前虚弱和肌肉减少的合并症相关因素。结果：114例患者获得有效资料。该患者群体中合并虚弱和肌肉减少症的患病率为25.44% %。Logistic回归分析显示，年龄较大、慢性病合并症较多、血红蛋白水平较低、社会支持减少是独立决定因素（p ）。结论：肝包虫病住院肝移植患者合并症虚弱和肌肉减少相对普遍。应进行全面的术前评估，以确定这些合并症，并应根据确定的决定因素迅速实施有针对性的干预策略，以减轻疾病进展。

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引用次数: 0

Case report: Recipient-derived, late-onset post-transplant lymphoproliferative disorder involving a transplanted liver 病例报告：受者来源，移植后迟发性淋巴细胞增生性疾病累及移植肝脏。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-09-12 DOI: 10.1016/j.trim.2025.102299

Dongmei Zou , Qiang Ma , Dandan Wang , Dongdong Lin , Hong Zhao , Wanling Sun

Introduction

Post-transplant lymphoproliferative disorders (PTLD) are severe complications of transplantation associated with poor outcomes. Compared to early-onset PTLDs, late-onset PTLDs are much less associated with allograft localization. Herein, we report a case of Epstein-Barr virus (EBV)-negative lymphoma involving a graft 7 years after liver transplantation.

Case presentation

A 45-year-old man presented with hepatomegaly 7 years after liver transplantation. Liver puncture biopsy revealed B-cell lymphoma with a high proliferation index and a germinal center B-cell-like subtype. Tissue and other donor information were unavailable. Next-generation sequencing was performed on the tumor and recipient tissues, and the single nucleotide polymorphism (SNP) sites were identical, thereby confirming the recipient origin. The patient received a reduction in immunosuppression and six cycles of rituximab, reduced doses of cyclophosphamide, doxorubicin, vincristine, and prednisone, and achieved complete remission after the fourth cycle of treatment. The patient remained in good condition for 7 months after the last chemotherapy dose.

Conclusion

This rare case report describes a late-onset EBV-negative recipient-derived PTLD involving a transplanted liver. SNP analysis is a useful method for determining tumor origin in situations where donor tissue is unavailable.

移植后淋巴细胞增生性疾病（PTLD）是移植术后的严重并发症，预后较差。与早发性PTLDs相比，晚发性PTLDs与同种异体移植物定位的相关性要小得多。在此，我们报告一例eb病毒（EBV）阴性淋巴瘤，涉及肝移植7 年后的移植物。病例介绍：45岁男性，肝移植后7 年出现肝肿大。肝脏穿刺活检显示高增殖指数的b细胞淋巴瘤和生发中心b细胞样亚型。无法获得组织和其他捐赠者的信息。对肿瘤和受体组织进行新一代测序，单核苷酸多态性（SNP）位点相同，从而确认受体来源。患者接受了免疫抑制的减少和6个周期的利妥昔单抗，减少了环磷酰胺、阿霉素、长春新碱和强的松的剂量，并在第4个周期的治疗后完全缓解。在最后一次化疗后，患者保持良好状态7 个月。结论：这个罕见的病例报告描述了一个迟发性ebv阴性受体与PTLD累及肝脏移植。在供体组织不可用的情况下，SNP分析是确定肿瘤起源的有用方法。

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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 : 2025-12-01 Epub 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

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 : 2025-12-01 Epub 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。

{"title":"Lung transplantation in patients with diabetes: A systematic review","authors":"Fatemeh Moosaie , Shiva Abedinzadeh , Sepide Javankiani , Fatemeh Asli , Prajjwol Luitel , Seyede Marzie Fatemi Abhari","doi":"10.1016/j.trim.2025.102279","DOIUrl":"10.1016/j.trim.2025.102279","url":null,"abstract":"<div><h3>Background and aim</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102279"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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 : 2025-12-01 Epub 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

ELAVL1-stabilized USP22 promotes diabetic nephropathy progression via mediating podocyte injury and death by triggering ACSL4 deubiquitination elavl1稳定的USP22通过触发ACSL4去泛素化介导足细胞损伤和死亡，从而促进糖尿病肾病的进展。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI: 10.1016/j.trim.2025.102280

Xin Wang , Wei Wang , MengYing Han , JingYuan Zhang , YaNan Li

Background

Diabetic nephropathy (DN) represents approximately 50 % of all chronic kidney disease cases. Given the established involvement of USP22 in DN progression, this study investigated its underlying regulatory mechanisms.

Methods

Mouse podocytes were treated with high glucose (HG), and a diabetic mouse model was established. Podocyte viability and apoptosis were assessed by CCK-8 and TUNEL/flow cytometry, respectively. Ferroptosis markers (Fe²⁺, ROS, MDA, and GSH) and inflammatory cytokines were quantified using ELISA and commercial kits per manufacturers' protocols. The interaction of USP22 with ACSL4 was demonstrated through protein stability and co-immunoprecipitation (Co-IP) assays. Additionally, RNA immunoprecipitation (RIP) and mRNA stability assays were employed to elucidate the ELAVL1/USP22 interaction.

Results

In HG-treated podocytes, USP22 silencing enhanced cell viability (P = 0.0018), repressed apoptosis (P = 0.0019), and reduced the release of inflammatory cytokines (IL-1β: P = 0.0002; TNF-α: P < 0.0001) and ferroptosis markers (Fe²⁺: P = 0.0002; ROS: P = 0.0005; MDA: P = 0.0017; GSH: P = 0.0086). Conversely, USP22 overexpression in HG-treated podocytes exhibited the opposite effects (P < 0.05). USP22 increased ACSL4 expression (P = 0.0012) in a deubiquitination-dependent manner. Notably, ACSL4 overexpression rescued USP22 depletion-mediated alterations on cell viability, apoptosis, inflammation, and ferroptosis (P < 0.05). Moreover, ELAVL1 stabilized USP22 mRNA through interaction (P = 0.0075). USP22 silencing alleviated DN progression and reduced inflammation cytokine secretion in a diabetic mouse model (P < 0.05).

Conclusion

ELAVL1-stabilized USP22 promotes DN progression by exacerbating podocyte injury and enhancing inflammatory responses and cell death through ACSL4 deubiquitination-dependent mechanisms.

背景：糖尿病肾病（DN）约占所有慢性肾病病例的50% %。鉴于USP22参与DN的进展，本研究探讨了其潜在的调控机制。方法：采用高糖处理小鼠足细胞，建立糖尿病小鼠模型。CCK-8和TUNEL/流式细胞术分别检测足细胞活力和凋亡。根据制造商的协议，使用ELISA和商业试剂盒对铁凋亡标志物（Fe2+、ROS、MDA和GSH）和炎症细胞因子进行定量。通过蛋白稳定性和共免疫沉淀（Co-IP）实验证实了USP22与ACSL4的相互作用。此外，采用RNA免疫沉淀（RIP）和mRNA稳定性分析来阐明ELAVL1/USP22的相互作用。结果:在HG-treated足细胞,USP22沉默增强细胞活力(P = 0.0018),压抑的细胞凋亡(P = 0.0019),并降低炎性细胞因子的释放(il - 1β:P = 0.0002;肿瘤坏死因子-α:P 2 +:P = 0.0002;活性氧:P = 0.0005;MDA: P = 0.0017;谷胱甘肽:P = 0.0086)。相反，在hg处理的足细胞中，USP22过表达表现出相反的作用(P 结论：elavl1稳定的USP22通过ACSL4去泛素化依赖机制加重足细胞损伤，增强炎症反应和细胞死亡，从而促进DN的进展。

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引用次数: 0

Characteristics linking ischemia-reperfusion to chronic lung allograft dysfunction in lung transplantation: A single-cell bioinformatics analysis 肺移植中缺血-再灌注与慢性同种异体肺移植物功能障碍相关的特征：单细胞生物信息学分析。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.trim.2025.102326

Peng Zhang , Zhendong Qiao , Song Zhao , Kai Wu

Background

Lung transplantation offers a life-saving procedure to patients with end-stage lung diseases with 85–89 % one year and 60 % five-year survival rates. Lung transplants are complicated by early ischemia/reperfusion injury (IRI) and late chronic lung allograft dysfunction (CLAD). However, the cellular and molecular links between IRI and CLAD remain unclear.

Materials and methods

We integrated single-cell RNA-seq results from GSE220797 and GSE224210 data sets. After quality filtering, we performed Louvain clustering and UMAP visualization. We applied Augur method to prioritize cell populations by transcriptional responsiveness to IRI and CLAD. We also performed dynamic trajectory analyses to map pseudotemporal transitions. Pathway activity was characterized by differential expression analysis and module scoring. Intercellular communication was assessed using CellChat and MEBOCOST analyses. Regulon inference was performed with pySCENIC analysis.

Results

Overall, epithelial cells showed progressive metabolic suppression and activation of cuproptosis, a programmed cell death (PCD) triggered by excessive copper accumulation within cells. Club cells, found in the small airways of the lungs, exhibited developmental plasticity and predictive potential across IRI and CLAD conditions. Among myeloid populations, M1 proinflammatory (AM_M1TM) macrophages underwent macrophage-to-myofibroblast transition (MMT) and produced excessive extracellular matrix (ECM) supporting a network of proteins surrounding cells. Metabolite and cell–cell communication analyses revealed declining macrophage/epithelial metabolic crosstalk and differential signaling flux from normal through IRI to CLAD transition.

Conclusions

The integrated single-cell atlas delineates interaction of multiple cells and their signaling pathways linking IRI to CLAD processes. These findings require further verification through studies in animal models and clinical samples.

背景：肺移植为终末期肺病患者提供了一种挽救生命的手术，其一年生存率为85-89 %，五年生存率为60 %。肺移植并发早期缺血/再灌注损伤（IRI）和晚期慢性同种异体肺功能障碍（CLAD）。然而，IRI和CLAD之间的细胞和分子联系尚不清楚。材料和方法：我们整合了来自GSE220797和GSE224210数据集的单细胞RNA-seq结果。经过质量过滤后，我们进行了Louvain聚类和UMAP可视化。我们应用Augur方法通过对IRI和CLAD的转录反应来确定细胞群的优先级。我们还进行了动态轨迹分析来映射伪时间转换。通过差异表达分析和模块评分来表征通路活性。使用CellChat和MEBOCOST分析评估细胞间通信。用pySCENIC分析进行规律推理。结果：总体而言，上皮细胞表现出进行性代谢抑制和铜增生的激活，这是一种由细胞内过量铜积累引发的程序性细胞死亡（PCD）。在肺小气道中发现的俱乐部细胞在IRI和CLAD条件下表现出发育可塑性和预测潜力。在髓系人群中，M1促炎（AM_M1TM）巨噬细胞经历巨噬细胞到肌成纤维细胞的转化（MMT），并产生过多的细胞外基质（ECM），支持细胞周围的蛋白质网络。代谢物和细胞间通讯分析显示，巨噬细胞/上皮代谢串音下降，从正常到IRI到CLAD转变的差异信号通量下降。结论：整合的单细胞图谱描述了多个细胞的相互作用及其连接IRI和CLAD过程的信号通路。这些发现需要通过动物模型和临床样本的研究进一步验证。

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引用次数: 0

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 : 2025-12-01 Epub 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

PD-1 inhibitor use for skin malignancies in patients with solid organ and bone marrow transplants: Graft rejection, treatment responses, and survival PD-1抑制剂用于实体器官和骨髓移植患者的皮肤恶性肿瘤：移植排斥反应，治疗反应和生存

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.trim.2025.102287

Lily M. Parker , Kate E. Beekman , Meredith E. Thomley , Rahul Mhaskar , Kenneth Tsai , Lilia M. Correa-Selm

Importance

Solid organ transplant recipients face a markedly increased risk of aggressive skin cancers. Programmed cell death protein-1 (PD-1) inhibitors have significantly improved outcomes for advanced melanoma, squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC), but their use in transplant patients is limited by the risk of graft rejection. Data in this population remain scarce.

Objective

To evaluate rates of graft rejection, treatment responses, and survival among transplant recipients treated with PD-1 inhibitors for advanced skin malignancies.

Methods

We identified 16 solid organ transplants patients (14 kidney, 2 liver) and 5 allogeneic bone marrow transplant patients. Skin cancer types included 14 squamous cell carcinomas, 2 melanomas, and 5 Merkel cell carcinomas.

Results

Among 16 solid organ transplant recipients (14 kidney, 2 liver), 4 developed graft rejection. Three occurred prior to PD-1 initiation, leaving only one rejection attributable to therapy. Median survival following PD-1 initiation was longer in patients with rejection (8.3 months) compared with those who died of cancer progression (3.0 months). No bone marrow transplant recipients experienced rejection.

Conclusions and relevance

In our data (the largest reported cohort to date), most transplant recipients tolerated PD-1 inhibitors without graft rejection. Although rejection remains a serious risk, these findings suggest that PD-1 immunotherapy may be considered as a salvage option for carefully selected patients with advanced skin cancer.

实体器官移植受者患侵袭性皮肤癌的风险明显增加。程序性细胞死亡蛋白-1 （PD-1）抑制剂可以显著改善晚期黑色素瘤、鳞状细胞癌（SCC）和默克尔细胞癌（MCC）的预后，但它们在移植患者中的应用受到移植物排斥反应风险的限制。这一人群的数据仍然很少。目的评价PD-1抑制剂治疗晚期皮肤恶性肿瘤患者的移植排斥反应率、治疗反应和生存率。方法对16例实体器官移植患者（肾14例，肝2例）和5例异体骨髓移植患者进行分析。皮肤癌类型包括14种鳞状细胞癌、2种黑色素瘤和5种默克尔细胞癌。结果16例实体器官移植受者（肾14例，肝2例）中，4例发生排斥反应。其中三例发生在PD-1启动之前，仅留下一例可归因于治疗的排斥反应。PD-1启动后的中位生存期（8.3个月）比死于癌症进展的患者（3.0个月）更长。骨髓移植受者没有出现排斥反应。结论和相关性在我们的数据中（迄今为止报道的最大队列），大多数移植受者耐受PD-1抑制剂而无移植排斥反应。尽管排斥反应仍然存在严重的风险，但这些发现表明，PD-1免疫疗法可能被认为是精心挑选的晚期皮肤癌患者的救助性选择。

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引用次数: 0