Transplant immunology最新文献_第6页

Effects of intravenous immunoglobulin (IVIG) treatment on BK viremia and BK virus-associated nephropathy (BKVN) in kidney transplant patients: A systematic review 静脉注射免疫球蛋白（IVIG）治疗肾移植患者BK病毒血症和BK病毒相关肾病（BKVN）的影响：一项系统综述

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-18 DOI: 10.1016/j.trim.2025.102288

Maryam Hassanian , Mojgan Mortazavi , Firouzeh Moeinzadeh

Background

There are limited approved therapeutic options for BK viremia management in kidney transplant patients. We performed the present study to investigate the effect of Intravenous immunoglobulin (IVIG) treatment on BK viremia and BK virus-associated nephropathy (BKVN) in kidney transplant patients.

Methods

A systematic search was performed in Web of Science, Embase, PubMed, and Scopus for studies that investigated the effect of IVIG therapy on BK viremia and BKVN in kidney transplant patients. Observational studies and case series were considered eligible for inclusion in this study. Data extraction was performed by two independent investigators by a standard checklist.

Findings

Our results indicated that IVIG treatment in patients with BKVN was effective in BK viremia treatment and nephropathy. In addition, preemptive IVIG significantly decreased the risk of BK viremia and BKVN in high-risk patients. However, it does not seem that IVIG treatment has a beneficial impact on allograft function. Because no significant improvement in serum levels of creatinine has been reported in previous studies. In addition, the presence of interstitial fibrosis or tubular atrophy was reported in studies with histopathological examinations of renal biopsies following IVIG treatment.

Conclusion

IVIG therapy combined with immunosuppression reduction may be beneficial in treating BK viremia and BKVN, but its impact on graft function and survival remains uncertain. Further studies are needed to clarify its role in kidney transplant outcomes.

背景：肾移植患者BK病毒血症的治疗方案有限。本研究旨在探讨静脉注射免疫球蛋白（IVIG）治疗肾移植患者BK病毒血症和BK病毒相关肾病（BKVN）的效果。方法：系统检索Web of Science、Embase、PubMed和Scopus中有关IVIG治疗肾移植患者BK病毒血症和BKVN的研究。观察性研究和病例系列被认为符合纳入本研究的条件。数据提取由两名独立调查员按照标准检查表进行。结果：我们的研究结果表明，IVIG治疗BKVN患者对BK病毒血症治疗和肾病有效。此外，预防性IVIG可显著降低高危患者发生BK病毒血症和BKVN的风险。然而，IVIG治疗似乎并没有对同种异体移植物功能产生有益的影响。因为在以前的研究中没有报道血清肌酐水平有显著改善。此外，在IVIG治疗后肾活检的组织病理学检查中报告了间质纤维化或小管萎缩的存在。结论：IVIG联合免疫抑制减少治疗BK病毒血症和BKVN可能有益，但对移植物功能和存活的影响尚不确定。需要进一步的研究来阐明其在肾移植结果中的作用。

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引用次数: 0

Oral cyclosporine a nanosuspension for improved immunosuppressive efficacy: In vivo cytokine profiling in rats 口服环孢素纳米混悬液改善免疫抑制效果：大鼠体内细胞因子谱。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-17 DOI: 10.1016/j.trim.2025.102301

Çağman Tan , Sıla Gülbağ Pınar , Nevin Çelebi

Background

Cyclosporine A (CycA) is a cornerstone immunosuppressant in transplantation, but its poor solubility and variable bioavailability limit therapeutic efficacy. Nanosuspension technology offers an innovative formulation strategy to enhance oral absorption and potentially improve immunomodulatory effects.

Methods

Wistar rats (n = 4/group) received oral CycA as coarse powder, physical mixture, commercial product, or nanosuspension. Serum cytokines and chemokines (IL-4, IL-5, IL-10, IL-13, IL-17 A, Eotaxin, GRO-α, IP-10, MCP-1, MCP-3, MIP-1α, MIP-2, Rantes) were quantified on days 7, 14, and 21. Data were expressed as mean ± SD. Statistical analysis was performed using Mann–Whitney U test with Benjamini–Hochberg correction for multiple comparisons.

Results

At day 21, IL-10 levels were significantly higher in the nanosuspension group compared to control and coarse powder (adjusted p = 0.041), confirming nanosuspension-mediated IL-10 upregulation. IL-13 was also elevated in nanosuspension and commercial product groups versus control (p_adj = 0.048). IL-4 was significantly reduced in the nanosuspension group at both day 7 (p_adj = 0.042) and day 21 (p_adj = 0.049). IL-5 levels increased in the nanosuspension group at day 21 compared to control and coarse powder (p_adj = 0.037). No statistically significant differences were detected for IL-17 A or chemokines, although descriptive trends suggested altered profiles in the nanosuspension group.

Conclusion

CycA nanosuspension selectively modulates cytokine networks by elevating IL-10, fine-tuning Th2 cytokines (IL-4, IL-5, IL-13), and trending toward chemokine regulation. These findings highlight nanosuspension technology as a promising strategy to enhance CycA's immunosuppressive efficacy, with potential implications for transplantation.

背景：环孢素A （Cyclosporine A, CycA）是移植中的基础免疫抑制剂，但其溶解度差和生物利用度多变限制了其治疗效果。纳米悬浮液技术提供了一种创新的配方策略，以增强口服吸收，并有可能改善免疫调节作用。方法：Wistar大鼠（n = 4只/组）口服CycA粗粉、物理混合物、商品产品和纳米混悬液。血清细胞因子和趋化因子（IL-4、IL-5、IL-10、IL-13、IL-17 A、Eotaxin、GRO-α、IP-10、MCP-1、MCP-3、MIP-1α、MIP-2、Rantes）在第7、14和21天进行定量。数据以平均值 ± SD表示。统计学分析采用Mann-Whitney U检验，多组比较采用Benjamini-Hochberg校正。结果：在第21天，与对照组和粗粉相比，纳米悬液组IL-10水平显著升高（调整p = 0.041），证实纳米悬液介导IL-10上调。与对照组相比，纳米混悬液和商业产品组IL-13也升高（p_adj = 0.048）。纳米悬浮液组IL-4在第7天（p_adj = 0.042）和第21天（p_adj = 0.049）均显著降低。与对照组和粗粉相比，纳米混悬液组IL-5水平在第21天升高（p_adj = 0.037）。IL-17 A或趋化因子未检测到统计学上的显著差异，尽管描述性趋势表明纳米悬浮液组的特征发生了改变。结论：CycA纳米悬浮液通过上调IL-10、微调Th2细胞因子（IL-4、IL-5、IL-13）、趋化因子调控等方式选择性调节细胞因子网络。这些发现突出了纳米悬液技术作为一种有前途的策略来增强CycA的免疫抑制效果，对移植有潜在的影响。

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引用次数: 0

Recurrent sarcoidosis in a transplanted kidney: A case report and literature review 移植肾复发性结节病1例报告并文献复习。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-16 DOI: 10.1016/j.trim.2025.102300

Abd Assalam Qannus , H. Tahsin Özpolat , Dory Salazar , Erica Bracamonte , Bekir Tanriover , Venkatesh Ariyamathu

Sarcoidosis is a multisystem inflammatory disorder that primarily affects the lungs. However, extra-pulmonary involvement, including the kidneys and heart, is also observed. Kidney involvement may manifest as hypercalcemia or as acute or chronic kidney injury, which could progress to end-stage kidney disease. Patients with sarcoidosis have been reported to successfully undergo kidney transplants, although some have experienced recurrence of sarcoidosis after the transplant, affecting both the kidneys and other organs. Here, we present a case of a patient who underwent a kidney transplant followed by the recurrence of sarcoidosis, which manifested as hypercalcemia five months after the transplant.

结节病是一种多系统炎症性疾病，主要影响肺部。然而，肺外受累，包括肾脏和心脏，也被观察到。肾脏受累可表现为高钙血症或急性或慢性肾损伤，可发展为终末期肾脏疾病。有报道称，结节病患者成功地接受了肾移植，尽管有些患者在移植后结节病复发，影响肾脏和其他器官。在此，我们报告一例接受肾移植后结节病复发的患者，移植后5个月表现为高钙血症。

引用次数: 0

De novo donor specific antibody (dnDSA) development with tacrolimus versus Belatacept based regimens in kidney transplant recipients 在肾移植受者中，他克莫司与基于Belatacept的方案的新供者特异性抗体（dnDSA）的发展。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-15 DOI: 10.1016/j.trim.2025.102297

Cayla Kass , Goni Katz-Greenberg , Jason Bodner , Scott Sanoff , Alice Parish , Alaattin Erkanli , Jennifer Byrns

Purpose

Belatacept has been associated with less de novo specific antibody (dnDSA) development, but few publications have compared the incidence of dnDSA development between tacrolimus and belatacept-based immunosuppression regimens. The purpose of this study was to investigate the differences in dnDSA development and clinical outcomes between these two maintenance regimens in kidney transplant.

Methods

This was a retrospective, single center, cohort study of patients transplanted between 2013 and 2019 who received a de novo belatacept or tacrolimus-based immunosuppression regimen. The primary outcome was the incidence of dnDSA development (MFI ≥ 1000) at 36 months. Secondary outcomes included renal function, biopsy proven rejection (BPAR), and patient/graft survival.

Results

Ninety patients met inclusion criteria. The primary outcome occurred in 4 (8.9 %) belatacept patients and 6 (13.3 %) tacrolimus patients, with an overall median time to dnDSA of 300 days (p = 0.51). Class II dnDSA development occurred in 3 (6.7 %) belatacept patients and 6 (13.3 %) tacrolimus patients. Belatacept patients had a lower, but not significantly different, rate of developing BPAR (4.4 % vs 13.3 %, p = 0.13) and had superior renal function at 36 months (median 66 ml/min vs 53 ml/min, p < 0.01). Overall, there was excellent patient/graft survival at 36 months post-transplant.

Conclusion

De novo belatacept use did not result in a statistically significant difference in the development of dnDSAs but did show a numerically lower class II dnDSA and BPAR development. Overall, belatacept was associated with improved renal function as compared to tacrolimus-based regimens.

目的：Belatacept与较少的新发特异性抗体（dnDSA）发生相关，但很少有文献比较他克莫司和基于Belatacept的免疫抑制方案之间dnDSA发生的发生率。本研究的目的是调查两种维持方案在肾移植中dnDSA发展和临床结果的差异。方法：这是一项回顾性、单中心、队列研究，研究对象是2013年至2019年间接受贝拉他普或他克莫司免疫抑制方案的移植患者。主要终点是36 个月时dnDSA发生的发生率（MFI ≥ 1000）。次要结局包括肾功能、活检证实的排斥反应（BPAR）和患者/移植物存活。结果：90例患者符合纳入标准。主要结局发生在4例（8.9 %）belatacept患者和6例（13.3 %）他克莫司患者中，到达dnDSA的总中位时间为300 天（p = 0.51）。II类dnDSA发生在3例（6.7 %）belataccept患者和6例（13.3 %）他克莫司患者中。Belatacept患者发生BPAR的比率较低，但没有显著差异（4.4 % vs 13.3 %,p = 0.13），并且在36 个月时具有较好的肾功能（中位值66 ml/min vs 53 ml/min， p ）。结论：重新使用Belatacept并没有导致dnDSA发展的统计学差异，但确实显示了较低的II级dnDSA和BPAR发展。总的来说，与以他克莫司为基础的方案相比，贝拉他普与肾功能改善有关。

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引用次数: 0

Assessing the influence of isolation techniques on NK cell transcriptomic profiles 评估分离技术对NK细胞转录组谱的影响。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-14 DOI: 10.1016/j.trim.2025.102298

Rana ElNouty , Ahmed Moustafa , Maha Mostafa , Amged Ouf , Khaled Abou-Aisha , Mona Rady

Natural Killer (NK) cells are vital components of the innate immune system, playing a crucial role in defending the body against tumors and virally infected cells. While various methods exist for their isolation, the profound impact of these techniques on NK cell biology remains poorly characterized.This study presents a comprehensive analysis of the transcriptomic profiles of NK cells isolated using different positive selection methods; anti-CD56, anti-CD7 (with two distinct lineage depletion protocols), and a combination of anti-CD16 and anti-CD56 antibodies, compared to negative selection using immunomagnetic beads. Our integrated analysis of RNA-Seq datasets revealed that the isolation method is a dominant source of transcriptomic variation, accounting for 68.6 % of the total dataset variance, with technical factors being inextricably confounded with this biological signal. We identified extensive method-specific transcriptional signatures, with minimal overlap (<0.1 %) in differentially expressed genes (DEGs) across techniques. Functional enrichment analysis demonstrated that these signatures correspond to starkly different functional states: anti-CD16/anti-CD56 selection enriched for a highly activated, cytotoxically competent NK cell population with upregulated pathways in cytotoxicity and immune surveillance, while one anti-CD7-based method captured NK cells in a suppressed state, showing significant downregulation of lymphocyte activation and cytotoxicity pathways. Marker expression analysis further revealed extreme inter-study heterogeneity, with fold-changes in key cytotoxic genes exceeding 70,000-fold between methods. These findings highlight that the choice of isolation technique is not neutral but fundamentally determines the transcriptional and functional identity of the studied NK cell population. Our results highlight the critical importance of methodological standardization in NK cell research and provide essential guidance for selecting isolation strategies tailored to specific research or therapeutic applications.

自然杀伤细胞（NK）是先天免疫系统的重要组成部分，在保护身体免受肿瘤和病毒感染细胞的侵害方面起着至关重要的作用。虽然存在各种方法来分离NK细胞，但这些技术对NK细胞生物学的深远影响仍然缺乏表征。本研究对使用不同阳性选择方法分离的NK细胞的转录组学特征进行了全面分析；与使用免疫磁珠的阴性选择相比，抗cd56，抗cd7（有两种不同的谱系耗尽方案），以及抗cd16和抗cd56抗体的组合。我们对RNA-Seq数据集的综合分析表明，分离方法是转录组变异的主要来源，占总数据集变异的68.6% %，技术因素与这种生物信号不可避免地混淆在一起。我们发现了广泛的方法特异性转录特征，重叠最小(

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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 : 2025-09-12 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

Racial and ethnic disparities in kidney transplantation 肾移植中的种族差异。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-09-10 DOI: 10.1016/j.trim.2025.102289

Macrae Kozody , Roberta Buccilli , Giovanni Faddoul , Jorge Ortiz

Social determinants of health, bias and genetic predisposition contribute to racial inequities in chronic kidney disease (CKD) and kidney transplant (KTX) allocation. Recognizing and addressing these complex factors leads to improvement in outcomes. This narrative review aims to discuss the current state of racial disparities surrounding KTX and identify where future efforts should be concentrated. The discussion focuses on data from the past 10 years (2015–2025). Overall mortality and graft loss is lowest in Hispanics and Asians and highest in Native Americans, perhaps due to the unique protective or detrimental social factors in these populations. Blacks have equal to better mortality than Whites, but worse graft survival. In an effort to identify paucities in the current literature, KTX outcomes by specific CKD etiologies are reviewed, including: diabetic nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis, vasculitis and polycystic kidney disease. Graft survival and mortality patterns for disease specific kidney transplant generally mirrors that of all cause KTX, but available data is limited. In recent years, racial disparities in CKD and transplant have improved, but still persist, representing the need for continued investigation and improvement. Future work should focus on continued identification and implementation of successful mitigation strategies and investigation where current literature is insufficient, such as diabetic nephropathy.

健康、偏见和遗传易感性的社会决定因素导致慢性肾脏疾病（CKD）和肾脏移植（KTX）分配中的种族不平等。认识和处理这些复杂的因素会导致结果的改善。这篇叙述性评论旨在讨论围绕KTX的种族差异的现状，并确定未来的努力应该集中在哪里。讨论的重点是过去10年 年（2015-2025）的数据。西班牙裔和亚洲人的总体死亡率和移植物损失最低，而美洲原住民最高，这可能是由于这些人群中独特的保护性或有害的社会因素。黑人的死亡率比白人高，但存活率却比白人差。为了找出目前文献中的不足之处，我们回顾了特定CKD病因的KTX结果，包括：糖尿病肾病、局灶节段性肾小球硬化、膜性肾病、狼疮性肾炎、血管炎和多囊肾病。特定疾病肾移植的移植物存活和死亡率模式通常反映了全因KTX，但可用的数据有限。近年来，CKD和移植中的种族差异有所改善，但仍然存在，这表明需要继续调查和改进。未来的工作应侧重于继续确定和实施成功的缓解策略，并调查目前文献不足的领域，如糖尿病肾病。

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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 : 2025-09-10 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

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 : 2025-09-08 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

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。

{"title":"Pre-donation statin therapy to improve solid organ transplant outcomes","authors":"Juhi R. Patel , John Dark , Daniel Harvey , Kulwant Dhadwal","doi":"10.1016/j.trim.2025.102283","DOIUrl":"10.1016/j.trim.2025.102283","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102283"},"PeriodicalIF":1.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021006","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}

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