Transplant immunology最新文献_第8页

The KIR/HLA class I co-expression and transplantation outcomes after HSCT/BMT from HLA-matched sibling donors 来自HLA匹配的同胞供者的HSCT/BMT后KIR/HLA I类共表达和移植结果

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-08-05 DOI: 10.1016/j.trim.2025.102274

Joanna Dębska-Zielkowska , Bartosz Słomiński , Hanna Zielińska , Anna Dukat-Mazurek , Grażyna Moszkowska , Maria Bieniaszewska , Jan Maciej Zaucha , Piotr Trzonkowski , Maciej Zieliński

Background

Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient.

Methods

We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [n = 24 with acute myeloid leukemia (AML), n = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and n = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors.

Results

Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD (p = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 × 10⁹ cells/L) under 28 days (p = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients (r = 0.9932).

Conclusion

Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.

背景：自然杀伤细胞（NK）表达杀伤免疫球蛋白样受体（KIRs），该受体调节NK细胞的功能。自体人白细胞抗原（HLA） I类分子作为kir的抑制分子，阻断NK细胞的杀伤活性。由于正常NK活性可能会影响来自HLA匹配的同胞供体的造血干细胞移植（HSCT）或骨髓移植（BMT）的结果，我们研究了NK细胞上呈现的kir和I类HLA之间的相互作用。移植受体体内I类HLA配体抑制剂表达不足可能导致移植物抗宿主病（GvHD）或移植排斥等并发症。方法：我们研究了缺失KIR配体（MSL）和KIR单倍型对HSCT患者GvHD发展、复发、死亡、感染和细胞恢复的影响。本组纳入59例患者[n = 24例急性髓性白血病（AML）， n = 12例慢性髓性白血病（CML）， n = 12例骨髓增生异常综合征（MDS）， n = 11例急性淋巴细胞白血病（ALL）]，他们接受了来自兄弟姐妹供体的HSCT/BMT。结果：我们的研究结果显示，单倍型AA在MDS患者的供体中比Bx更常见，并且与慢性(c) GvHD的发生率较高相关（p = 0.003）。在该组中，我们还观察到AA供体单倍型与28 天内0.5 G/l（0.5 × 109个细胞/l）绝对中性粒细胞计数重建之间存在统计学意义（p = 0.03）。我们的结果还显示AML患者的KIR MSL值与cGvHD有很好的相关性（r = 0.9932）。结论：在选择相关供体阶段进行KIR/HLA I类分析对血液学移植的结果有影响，并可能减少并发症。

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引用次数: 0

Regulatory B cells: Synergistic cellular mechanisms and therapeutic potential for alleviating transplant rejection 调节性B细胞：减轻移植排斥反应的协同细胞机制和治疗潜力

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-08-05 DOI: 10.1016/j.trim.2025.102277

Shaochen Yu , Mengjie Zhang , Ziyue Dou , Jian Lu

Posttransplantation rejection remains a critical challenge in organ transplantation. While immunosuppressants improve graft survival, their long-term side effects compromise patient quality of life, necessitating novel, side effect-free strategies to reduce the incidence of rejection. Regulatory B cells (Bregs), an immunomodulatory B lymphocyte subset within the immune microenvironment, have the potential to mitigate transplant rejection. However, Bregs alone are insufficient to control rejection, and their suppressive effects are notably limited in the absence of immunosuppression, highlighting their dependence on synergistic interactions with other regulatory mechanisms. This review summarizes the diverse phenotypes of Bregs and elucidates their immunomodulatory mechanisms, with a focus on cellular interactions (e.g., with Tregs, macrophages, dendritic cells, and NK cells) and cytokine secretion (e.g., IL-10, TGF-β, and IL-35). We critically evaluate animal and clinical trial data concerning the role of Bregs in transplantation, discussing their potential as therapeutic targets and the current limitations and future directions for harnessing Bregs to alleviate transplant rejection.

移植后排斥反应仍然是器官移植的一个重要挑战。虽然免疫抑制剂可以提高移植物的存活率，但其长期副作用会影响患者的生活质量，因此需要新的无副作用的策略来减少排斥反应的发生率。调节性B细胞（Bregs）是免疫微环境中的一种免疫调节B淋巴细胞亚群，具有减轻移植排斥反应的潜力。然而，单独的Bregs不足以控制排斥反应，并且在缺乏免疫抑制的情况下，它们的抑制作用明显有限，突出了它们依赖于与其他调节机制的协同相互作用。本文综述了Bregs的多种表型，并阐明了它们的免疫调节机制，重点关注细胞相互作用（如与Tregs、巨噬细胞、树突状细胞和NK细胞）和细胞因子分泌（如IL-10、TGF-β和IL-35）。我们批判性地评估了关于Bregs在移植中的作用的动物和临床试验数据，讨论了它们作为治疗靶点的潜力，以及利用Bregs缓解移植排斥反应的当前局限性和未来方向。

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引用次数: 0

Risk factors for acute rejection in pediatric kidney transplantation 儿童肾移植急性排斥反应的危险因素。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-29 DOI: 10.1016/j.trim.2025.102273

Roman Gorchs , Matt Stout , Brooke Cohen , Jaden Ju , Eileen Brewer , Nhu Thao Nguyen Galván , Abbas Rana

Background

Acute rejection in pediatric kidney transplant patients can increase posttransplant costs and lead to limited survival of the graft. Identifying key risk factors for acute rejection in pediatric kidney recipients may allow for physicians to better tailor immunosuppressant regimens and decrease the occurrence of acute rejection.

Methods

A retrospective analysis was performed using kidney transplantation data provided by the United Network for Organ Sharing (UNOS) for patients younger than 18 years old who received their first kidney transplant between January 2005 and December 2022. The resulting study population consisted of 10,126 patients over the 18-year span. Risk factors for acute rejection in the first year post-transplant were identified using a multivariate analysis.

Results

Several variables were found to be statistically significant risk factors for acute rejection, including donor age ≤ 10 (Odds Ratio 1.44), Obese BMI (BMI-for-age z-score > 2.0), (Odds Ratio 1.22), a 6 Human Leukocyte Antigen (HLA) mismatch (Odds Ratio 1.22) and recipient age between 15 and 18 (Odds Ratio 1.21). Multiple factors were found to be protective, including male sex (Odds Ratio 0.85) and recipient age between 5 and 10 (Odds Ratio 0.79).

Conclusions

The results indicate several significant risk factors such as the recipient age, Body Mass Index, sex and the number of HLA mismatches between the donor and the recipient. Physicians should consider these factors when personalizing immunosuppressive regimens for pediatric kidney transplant patients.

背景：儿童肾移植患者的急性排斥反应会增加移植后的费用并导致移植物的有限存活。确定儿童肾受体急性排斥反应的关键危险因素可以使医生更好地定制免疫抑制方案，减少急性排斥反应的发生。方法：利用联合器官共享网络（UNOS）提供的肾移植数据，对2005年1月至2022年12月期间接受首次肾移植的18岁以下 患者进行回顾性分析。最终的研究人群包括10126名患者，时间跨度为18年。使用多变量分析确定移植后第一年急性排斥反应的危险因素。结果：发现几个变量是急性排斥反应的有统计学意义的危险因素，包括供体年龄 ≤ 10（比值比1.44）、肥胖BMI (BMI-for-age z-score > 2.0)（比值比1.22）、6人白细胞抗原（HLA）不匹配（比值比1.22）和受体年龄在15 - 18岁之间（比值比1.21）。发现多重因素具有保护作用，包括男性（优势比0.85）和受体年龄在5至10岁之间（优势比0.79）。结论：受者年龄、体质指数、性别、供者与受者HLA错配次数等因素均有明显危险。医生在为儿童肾移植患者个性化免疫抑制方案时应考虑这些因素。

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引用次数: 0

The clinical significance of CD45RA+FOXP3low naïve and CD45RA−FOXP3high effector/memory Treg subsets in the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation CD45RA+FOXP3low naïve和CD45RA−FOXP3high - effector/memory Treg亚群在异基因造血干细胞移植后急性移植物抗宿主病发生中的临床意义

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-29 DOI: 10.1016/j.trim.2025.102272

Mani Ramzi , Mohammadnabi Sanaei , Maryam Hesamadini , Hossein Golmoghaddam , Mehdi Kalani , Nargess Arandi

Introduction

It has been proposed that regulatory T cells (Tregs) might be involved in the induction of transplantation tolerance after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the role of Treg subsets in allo-HSCT outcomes, including the development of acute graft-versus-host disease (aGVHD). Herein, we assessed for the first time the association between the frequency of regulatory T cell (Treg) subsets, including CD45RA⁺FOXP3^low naïve (nTregs) and CD45RA⁻FOXP3^high effector/memory Tregs (eTregs), and aGVHD occurrence during 90 days after allo-HSCT.

Methods

Twenty-four pairs of donors/recipients with hematologic malignancies who underwent HLA-matched allo-HSCT were enrolled. The frequencies of nTregs and eTregs were determined via four-color flow cytometry.

Results

Compared with non-aGVHD patients, aGVHD patients had a lower frequency of nTregs in their donors (*P = 0.016). The reconstitution rate of nTregs was significantly slower on day +60 post-allo-HSCT in aGVHD patients than in non-aGVHD patients (*P = 0.025).

Patients who received grafts with nTregs<0.19 and a median frequency of nTregs<0.13 and eTregs<0.58 on day +30 after transplantation presented a relatively high cumulative incidence of aGVHD (*P = 0.039, *P = 0.032, and *P = 0.036, respectively). Multivariate analysis revealed that a low median total number of Tregs recovered on days +30 and + 60 post-allo-HSCT was associated with an increased incidence of aGVHD [HR = 0.199, 95 % CI, 0.041–0.969; *P = 0.046 and HR = 0.092, 95 % CI, 0.011–0.765; *P = 0.026, respectively].

Conclusion

This study provides novel insights showing that high donor nTreg content and rapid recovery of nTregs and eTregs early on day 30 post-transplantation are closely linked to protection from aGVHD.

有研究认为，调节性T细胞（Tregs）可能参与了异基因造血干细胞移植（alloo - hsct）后移植耐受的诱导。然而，对于Treg亚群在同种异体造血干细胞移植结果中的作用，包括急性移植物抗宿主病（aGVHD）的发展，我们知之甚少。在此，我们首次评估了调节性T细胞（Treg）亚群的频率，包括CD45RA+FOXP3low naïve （nTregs）和CD45RA−FOXP3high effector/memory Tregs (eTregs)，与alloo - hsct后90天aGVHD发生之间的关系。方法入选24对恶性血液病供体/受体，接受hla匹配的同种异体造血干细胞移植。通过四色流式细胞术检测nTregs和eTregs的频率。结果与非aGVHD患者相比，aGVHD患者供体中出现nTregs的频率较低（*P = 0.016）。与非aGVHD患者相比，aGVHD患者在同种异体造血干细胞移植后第60天的nTregs重构率显著降低（*P = 0.025）。移植后第30天nTregs<；0.19，中位频率为nTregs<；0.13，中位频率为eTregs<；0.58的患者，aGVHD的累积发病率相对较高（*P = 0.039, *P = 0.032, *P = 0.036）。多因素分析显示，同种异体造血干细胞移植后+30和+ 60天恢复的Tregs中位数较低与aGVHD发病率增加相关[HR = 0.199, 95% CI, 0.041-0.969；*P = 0.046, HR = 0.092, 95% CI, 0.011-0.765；*P = 0.026]。结论本研究提供了新的见解，表明高供体nTreg含量和移植后30天早期nTreg和etreg的快速恢复与aGVHD的保护密切相关。

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引用次数: 0

Safety and efficacy of high-dose versus standard-dose influenza vaccines in hematopoietic stem cell transplant recipients: A meta-analysis of randomized controlled trials 高剂量与标准剂量流感疫苗在造血干细胞移植受者中的安全性和有效性：一项随机对照试验的荟萃分析

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-29 DOI: 10.1016/j.trim.2025.102270

Ananda Pipphali Vidya , Nicholas Jason Wijaya , Dhabitah Zahraa Puteri Gathmir , Naira Ayesha Kayla Kornel , Muhammad Farhan , Imelda Rosalyn Sianipar

Given the vulnerability of hematopoietic cell transplant (HCT) patients to influenza infection and its complications, annual vaccination is recommended. However, vaccination was known to be less effective in these patients. Multiple studies have assessed various effects in HCT recipients after receiving different vaccine doses. However, the results have been inconclusive. This meta-analysis aims to provide a comprehensive analysis of the effectiveness and safety of HCT recipients when they receive a higher and standard dose of influenza vaccines. This study used PRISMA guidelines on several databases until Oct 25, 2024. We used ROB 2.0 and Review Manager 5.4 Software for further analysis. We included four low-risk of bias studies, and we conducted further analysis. The efficacy of HAI titer

\geq

1:40, >4-fold, and confirmed influenza positives was comparable in both groups, with insignificant results in each follow-up group. However, the adverse effect was found significantly higher in the high-dose group, specifically the local adverse effect (p < 0.0001). High-dose influenza vaccines showed higher adverse events and more confirmed influenza cases than standard-dose, suggesting standard-dose may be preferable post-HCT. These findings underscore the need for further research, particularly in diverse populations and vulnerable groups.

鉴于造血细胞移植（HCT）患者对流感感染及其并发症的脆弱性，建议每年接种疫苗。然而，已知疫苗接种对这些患者的效果较差。多项研究评估了不同疫苗剂量对HCT受者的不同影响。然而，研究结果尚无定论。本荟萃分析旨在全面分析HCT受者在接受更高剂量和标准剂量流感疫苗时的有效性和安全性。该研究在2024年10月25日之前使用了几个数据库的PRISMA指南。我们使用ROB 2.0和Review Manager 5.4软件进行进一步分析。我们纳入了4项低风险偏倚研究，并进行了进一步分析。血凝素滴度≥1:40、4倍、流感确诊阳性两组疗效具有可比性，各随访组结果均不显著。然而，高剂量组的不良反应明显更高，特别是局部不良反应(p <；0.0001)。与标准剂量相比，高剂量流感疫苗显示出更高的不良事件和更多的确诊流感病例，这表明标准剂量可能是hct后更可取的。这些发现强调了进一步研究的必要性，特别是在不同人群和弱势群体中。

{"title":"Safety and efficacy of high-dose versus standard-dose influenza vaccines in hematopoietic stem cell transplant recipients: A meta-analysis of randomized controlled trials","authors":"Ananda Pipphali Vidya , Nicholas Jason Wijaya , Dhabitah Zahraa Puteri Gathmir , Naira Ayesha Kayla Kornel , Muhammad Farhan , Imelda Rosalyn Sianipar","doi":"10.1016/j.trim.2025.102270","DOIUrl":"10.1016/j.trim.2025.102270","url":null,"abstract":"<div><div>Given the vulnerability of hematopoietic cell transplant (HCT) patients to influenza infection and its complications, annual vaccination is recommended. However, vaccination was known to be less effective in these patients. Multiple studies have assessed various effects in HCT recipients after receiving different vaccine doses. However, the results have been inconclusive. This meta-analysis aims to provide a comprehensive analysis of the effectiveness and safety of HCT recipients when they receive a higher and standard dose of influenza vaccines. This study used PRISMA guidelines on several databases until Oct 25, 2024. We used ROB 2.0 and Review Manager 5.4 Software for further analysis. We included four low-risk of bias studies, and we conducted further analysis. The efficacy of HAI titer <span><math><mo>≥</mo></math></span> 1:40, >4-fold, and confirmed influenza positives was comparable in both groups, with insignificant results in each follow-up group. However, the adverse effect was found significantly higher in the high-dose group, specifically the local adverse effect (<em>p</em> < 0.0001). High-dose influenza vaccines showed higher adverse events and more confirmed influenza cases than standard-dose, suggesting standard-dose may be preferable post-HCT. These findings underscore the need for further research, particularly in diverse populations and vulnerable groups.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102270"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749572","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

Successful use of belumosudil in a patient with chronic ocular GVHD: A case report 白莫硫地尔成功治疗慢性眼移植物抗宿主病1例。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-29 DOI: 10.1016/j.trim.2025.102271

Xiaoli Lv , Huibo Li , Zhijian Li , Di Jin , Fei Leng , Jie Liu , Dan Guo , Shengjin Fan , Sheng Su

Background

Belumosudil is a selective ROCK2 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients who have failed at least two prior systemic therapies. By inhibiting ROCK2, Belumosudil can down-regulate the secretion of IL-21 and IL-17, and up-regulate regulatory T cells (Tregs), which serve to attenuate the inflammatory response. In addition, it can act as an antifibrotic by inhibiting the Rho-ROCK-MRTF pathway, as well as down-regulating the expression of pro-fibrotic genes and TGF-β signaling. Selective inhibition of ROCK2 also reduces M2-like macrophages and choroidal neovascularization, which further exerts antifibrotic effects. Therefore, belumosudil shows great potential in the treatment of chronic Graft-Versus-Host-Disease (cGVHD).

Case presentation

We report the clinical course of a 39-year-old man with severe progressive chronic ocular GVHD (oGVHD), who showed significant improvement in ocular surface damage, including damage to the cornea and meibomian glands, as well as dry eye symptoms, after oral administration of belumosudil. Corneal leukoplakia and neovascularization were significantly reduced after treatment. Moreover, the patient's ocular surface symptoms remained stable without deterioration after cataract surgery. The patient's quality of life was significantly enhanced.

Conclusion

We report the clinical outcomes of a patient with chronic oGVHD treated with belumosudil. The patient's clinical symptoms significantly improved, especially inflammation of the meibomian gland, corneal leukoplakia, and neovascularization. This highlights its application value in patients with cGVHD and provides a promising treatment option for patients with oGVHD.

背景：Belumosudil是美国食品和药物管理局（FDA）批准的一种选择性ROCK2抑制剂，用于治疗至少两次系统性治疗失败的患者。Belumosudil通过抑制ROCK2，下调IL-21和IL-17的分泌，上调调节性T细胞（regulatory T cells, Tregs），起到减轻炎症反应的作用。此外，它可以通过抑制Rho-ROCK-MRTF通路，下调促纤维化基因表达和TGF-β信号传导，起到抗纤维化的作用。选择性抑制ROCK2还可减少m2样巨噬细胞和脉络膜新生血管，从而进一步发挥抗纤维化作用。因此，白莫硫地尔在治疗慢性移植物抗宿主病（cGVHD）方面显示出巨大的潜力。病例介绍：我们报告了一名患有严重进行性慢性眼部GVHD （oGVHD）的39岁男性患者的临床过程，口服白莫舒地尔后，患者的眼表损伤，包括角膜和睑板腺的损伤以及干眼症状均有显著改善。治疗后角膜白斑和新生血管明显减少。此外，白内障手术后患者的眼表症状保持稳定，没有恶化。患者的生活质量明显提高。结论：我们报告了一例慢性oGVHD患者使用白莫硫地尔治疗的临床结果。患者的临床症状明显改善，尤其是睑板腺炎症、角膜白斑和新生血管。这突出了其在cGVHD患者中的应用价值，为oGVHD患者提供了一种有希望的治疗选择。

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引用次数: 0

Pre-transplant sensitization and its effect on heart transplant rejection and survival outcomes 移植前致敏及其对心脏移植排斥反应和生存结局的影响。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-22 DOI: 10.1016/j.trim.2025.102264

Kyung-Hwa Shin , Soo Yong Lee , Min Ho Ju , Hyun-Ji Lee

Background

Sensitization of heart transplant (HT) recipients increases the risk of rejection. Assessment of sensitization using a calculated panel reactive antibody (cPRA) is crucial for evaluating transplant compatibility and predicting outcomes. This study investigated the impact of cPRA and pre-existing and de novo Human Leukocyte Antigen (HLA)-donor-specific antibodies (DSAs) on HT outcomes and aimed to identify recipients at a high risk of rejection.

Methods

This retrospective study included 121 adult recipients of HT from a single institution (2014–2023). cPRA values, flow cytometric crossmatches (FCXM), and DSAs were analyzed for their associations with antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR).

Results

Among the 121 HT recipients, 51.2 % experienced TCMR and 7.4 % experienced AMR. cPRA (I) ≥ 50 % was significantly associated with AMR, pre-existing DSA (pDSA), and positive FCXM. pDSA was present in 16.5 % of HT recipients and correlated with AMR but not mortality. De novo DSAs frequently emerged in 38 % of the recipients following TCMR episodes. Higher cPRA (I) levels correlated with increased rejection risk and shorter AMR-free survival.

Conclusions

High cPRA (≥50 %) significantly predicted the risk of AMR and correlated with pDSA and positive FCXM results. Pre-transplant cPRA assessment is crucial for identifying high-risk recipients and optimizing management strategies to improve HT outcomes.

背景：心脏移植（HT）受者的敏感性增加了排斥反应的风险。使用计算的面板反应性抗体（cPRA）评估致敏性对于评估移植相容性和预测结果至关重要。本研究调查了cPRA和预先存在的和新生的人类白细胞抗原（HLA）供体特异性抗体（dsa）对HT结果的影响，旨在识别排斥反应高风险的受体。方法：本回顾性研究包括来自同一机构（2014-2023年）的121名成人HT接受者。分析cPRA值、流式细胞交叉匹配（FCXM）和dsa与抗体介导的排斥反应（AMR）和T细胞介导的排斥反应（TCMR）的关系。结果：121名HT受体中，51.2% %发生TCMR， 7.4% %发生AMR。cPRA (I) ≥ 50 %与AMR、已存在的DSA （pDSA）和FCXM阳性显著相关。16.5% %的HT受体存在pDSA，与AMR相关，但与死亡率无关。在TCMR发作后，38% %的受者经常出现新的dsa。较高的cPRA (I)水平与排斥风险增加和无amr生存期缩短相关。结论：高cPRA（≥50 %）可显著预测AMR风险，并与pDSA和FCXM阳性结果相关。移植前cPRA评估对于识别高风险受体和优化管理策略改善HT结果至关重要。

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引用次数: 0

Effect of maintenance immunosuppressive therapy on FoxP3 and CD28 gene expression in low risk kidney transplant recipients 维持性免疫抑制治疗对低危肾移植受者FoxP3和CD28基因表达的影响

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-20 DOI: 10.1016/j.trim.2025.102268

May A. Hassaballa , Mariam Onsy F. Hanna , Ahmed Mohamed Radwan , Noussa M. ElAdawi , Amal Kamal Helmy , Tarek Fayad , Mervat ElAnsary , Gamal Saadi

Background

FoxP3 is a transcription factor expressed by regulatory T cells and is essential for their development and suppressive function. CD28 is a costimulatory receptor on T cells that binds to CD80 and CD86 on antigen-presenting cells, providing a signal required for T cell activation and survival. This study compared FoxP3 and CD28 gene expression in kidney transplant recipients (KTR) maintained on immunosuppressive therapy with mammalian target of rapamycin inhibitors (mTORI) versus calcineurin inhibitors (CNI).

Methods

The expression of FoxP3 and CD28 was assessed in immunologically low-risk KTR with stable graft function. KTR receiving CNI (n = 24) were compared with those who underwent early conversion to mTORI post-transplant (n = 20). All patients received a transplant from living donors and the median time since transplant was 60 months. Gene expression analysis was performed in the peripheral blood mononuclear cells by quantitative PCR.

Results

FoxP3 expression differed significantly between treatment groups, with higher levels observed in the mTORI group compared to the CNI group (P = 0.025), while CD28 expression was comparable between groups. Among KTR receiving CNI therapy, FoxP3 expression was significantly lower in female recipients compared to males (P = 0.008); this difference was not observed in the mTORI group. In a multivariate analysis including age, sex, FoxP3 expression and immunosuppressive therapy, only mTORI therapy was significantly associated with higher estimated glomerular filtration rate [β = 22.66 (95 % CI = 3.41–41.91), P = 0.022].

Conclusions

In stable KTR, long-term immunosuppression with mTORI is associated with higher FoxP3 expression and lower CD28 to FoxP3 expression ratio compared to CNI. Although FoxP3 expression differed between treatment groups, only mTORI therapy was independently associated with improved kidney function.

背景：FoxP3是调节性T细胞表达的转录因子，对T细胞的发育和抑制功能至关重要。CD28是T细胞上的共刺激受体，与抗原呈递细胞上的CD80和CD86结合，提供T细胞活化和存活所需的信号。本研究比较了长期肾移植受者（KTR）在哺乳动物靶向雷帕霉素抑制剂（mTORI）和钙调磷酸酶抑制剂（CNI）免疫抑制治疗下的FoxP3和CD28基因表达。方法：在移植功能稳定的免疫低危KTR中检测FoxP3和CD28的表达。接受CNI的KTR （n = 24）与移植后早期转换为mTORI的KTR （n = 20）进行比较。所有患者都接受了活体供体的移植，移植后的中位时间为60 个月。采用定量PCR方法对外周血单核细胞进行基因表达分析。结果：各治疗组间FoxP3表达差异有统计学意义，mTORI组FoxP3表达高于CNI组（P = 0.025），而CD28表达组间具有可比性。在接受CNI治疗的KTR患者中，女性患者FoxP3表达明显低于男性（P = 0.008）；在mTORI组中没有观察到这种差异。在包括年龄、性别、FoxP3表达和免疫抑制治疗在内的多变量分析中，只有mTORI治疗与较高的肾小球滤过率有显著相关[β = 22.66(95 % CI = 3.41-41.91),P = 0.022]。结论：在稳定的KTR中，与CNI相比，mTORI长期免疫抑制与FoxP3表达升高和CD28 / FoxP3表达比降低相关。虽然FoxP3表达在治疗组之间存在差异，但只有mTORI治疗与肾功能改善独立相关。

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引用次数: 0

Long-term outcomes of ABO-incompatible kidney transplantation in Argentina: A 10-years single-center experience 阿根廷abo血型不相容肾移植的长期结果：10年单中心研究

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-19 DOI: 10.1016/j.trim.2025.102266

Carlos Chiurchiu , Pehuén Fernández , Walter Douthat , Javier de Arteaga , Esteban Metrebian , Raul Colla , Alejandro Martinez Colombres , Guillermo Paladini , Juan Carlos Damonte , Virginia Damonte , Luciana Mas , Emanuel José Saad , Jorge de la Fuente

Introduction

ABO-incompatible (ABOi) kidney transplantation is a feasible option for patients without ABO-compatible (ABOc) living donors. However, its impact on rejection rates and long-term outcomes remains debated. This study aims to compare rejection incidence, graft survival, and patient outcomes between ABOi and ABOc kidney transplant recipients.

Methods

We conducted a retrospective, observational, analytical cohort study at the Hospital Privado Universitario de Córdoba, including all ABOi living donor kidney transplants performed between July 2014 and August 2024. For each ABOi recipient, an ABOc counterpart was matched based on age (±5 years), transplant date (±1 year), and sex (when possible). Patients were followed for up to 10 years post-transplant. Immunosuppressive protocols and infectious prophylaxis followed institutional guidelines.

Results

Of 217 living donor kidney transplants, 33 (15.2 %) were ABOi. No significant differences were found between ABOi and ABOc groups in demographic or clinical baseline characteristics, except for donor age (p = 0.026). There were no differences in graft function, major complications, graft loss, or mortality between groups. Acute rejection occurred in 11 ABOi patients (9 humoral, 2 cellular) and 10 ABOc patients (5 humoral, 4 cellular, 1 mixed), with no significant differences. The 10-year overall patient survival was 82.8 % for ABOi and 83.7 % for ABOc, while death-censored graft survival was 96.4 % and 91.7 %, respectively. The non-use of thymoglobulin was the only independent predictor of rejection (aOR = 5.44; 95 % CI = 1.16–25.5; p = 0.031).

Conclusion

ABOi kidney transplantation demonstrates comparable long-term outcomes to ABOc transplantation. It is a viable and safe alternative for patients lacking ABO-compatible living donors.

摘要：ABO-compatible （ABOi）肾移植对于没有ABO-compatible （ABOc）活体供者的患者是一种可行的选择。然而，它对拒绝率和长期结果的影响仍存在争议。本研究旨在比较ABOi和ABOc肾移植受者的排斥发生率、移植物存活率和患者预后。方法：我们在Privado Universitario de Córdoba医院进行了一项回顾性、观察性、分析性队列研究，包括2014年7月至2024年8月期间进行的所有ABOi活体肾脏移植。对于每个ABOi受者，根据年龄（±5 岁）、移植日期（±1 年）和性别（如果可能）匹配ABOc配对者。患者在移植后随访10 年。免疫抑制方案和感染预防遵循机构指导方针。结果：217例活体肾移植中，33例（15.2% %）为ABOi。除供体年龄外，ABOi组和ABOc组在人口统计学或临床基线特征方面无显著差异（p = 0.026）。两组间移植物功能、主要并发症、移植物损失或死亡率均无差异。11例ABOi患者（9例体液性，2例细胞性）发生急性排斥反应，10例ABOc患者（5例体液性，4例细胞性，1例混合）发生急性排斥反应，差异无统计学意义。ABOi的10年总生存率为82.8 %，ABOc的10年总生存率为83.7 %，而死亡审查的移植物生存率分别为96.4 %和91.7 %。不使用胸腺球蛋白是排斥反应的唯一独立预测因子(aOR = 5.44；95 % CI = 1.16 - -25.5; = 0.031页)。结论：ABOi肾移植与ABOc肾移植的远期疗效相当。对于缺乏abo相容活体供体的患者，这是一种可行且安全的替代方案。

{"title":"Long-term outcomes of ABO-incompatible kidney transplantation in Argentina: A 10-years single-center experience","authors":"Carlos Chiurchiu , Pehuén Fernández , Walter Douthat , Javier de Arteaga , Esteban Metrebian , Raul Colla , Alejandro Martinez Colombres , Guillermo Paladini , Juan Carlos Damonte , Virginia Damonte , Luciana Mas , Emanuel José Saad , Jorge de la Fuente","doi":"10.1016/j.trim.2025.102266","DOIUrl":"10.1016/j.trim.2025.102266","url":null,"abstract":"<div><h3>Introduction</h3><div>ABO-incompatible (ABOi) kidney transplantation is a feasible option for patients without ABO-compatible (ABOc) living donors. However, its impact on rejection rates and long-term outcomes remains debated. This study aims to compare rejection incidence, graft survival, and patient outcomes between ABOi and ABOc kidney transplant recipients.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, observational, analytical cohort study at the Hospital Privado Universitario de Córdoba, including all ABOi living donor kidney transplants performed between July 2014 and August 2024. For each ABOi recipient, an ABOc counterpart was matched based on age (±5 years), transplant date (±1 year), and sex (when possible). Patients were followed for up to 10 years post-transplant. Immunosuppressive protocols and infectious prophylaxis followed institutional guidelines.</div></div><div><h3>Results</h3><div>Of 217 living donor kidney transplants, 33 (15.2 %) were ABOi. No significant differences were found between ABOi and ABOc groups in demographic or clinical baseline characteristics, except for donor age (<em>p</em> = 0.026). There were no differences in graft function, major complications, graft loss, or mortality between groups. Acute rejection occurred in 11 ABOi patients (9 humoral, 2 cellular) and 10 ABOc patients (5 humoral, 4 cellular, 1 mixed), with no significant differences. The 10-year overall patient survival was 82.8 % for ABOi and 83.7 % for ABOc, while death-censored graft survival was 96.4 % and 91.7 %, respectively. The non-use of thymoglobulin was the only independent predictor of rejection (aOR = 5.44; 95 % CI = 1.16–25.5; <em>p</em> = 0.031).</div></div><div><h3>Conclusion</h3><div>ABOi kidney transplantation demonstrates comparable long-term outcomes to ABOc transplantation. It is a viable and safe alternative for patients lacking ABO-compatible living donors.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102266"},"PeriodicalIF":1.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683201","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

Syngeneic hematopoietic stem cell transplantation from an identical twin sister in an AML patient: “A case report highlighting accelerated engraftment and reduced transfusion requirements” 来自同卵双胞胎姐妹的同基因造血干细胞移植在AML患者中的应用：“一个强调加速移植和减少输血需求的病例报告”

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-07-16 DOI: 10.1016/j.trim.2025.102267

Ehsan Yazdandoust , Abbas Hajifathali , Zeinab Kaboli , Sedigheh Amini-Kafiabad

Background and objective

Hematopoietic stem cell transplantation (HSCT) is among the most effective immunotherapeutic strategies for treating hematologic malignancies in both pediatric and adult patients. Its global use has been steadily increasing. Patients undergoing HSCT commonly require transfusion support with blood products until engraftment is achieved, and transfusion requirements can significantly affect post-transplant outcomes. Despite advancements that have improved survival rates, transplant-related mortality (TRM) continues to be a major obstacle to optimal outcomes.

Case presentation

We present the case of a 46-year-old woman diagnosed with acute myeloid leukemia (AML) harboring an FLT3-ITD mutation, who underwent allogeneic HSCT. The donor was her identical twin sister, with full HLA compatibility (a 10/10 match) and an identical ABO blood group (O positive). Notably, the patient exhibited rapid neutrophil and platelet engraftment by day +9, which is earlier than typically observed in transplants from fully matched related or unrelated donors. Furthermore, the patient did not require any red blood cell or platelet transfusions during the transplantation period and developed no signs of acute or chronic graft-versus-host disease (GVHD). She has remained disease-free with no evidence of relapse for over three years post-transplant.

Conclusion

HSCT from an identical twin donor may provide favorable clinical outcomes, including accelerated engraftment and reduced transfusion needs during the transplantation process.

背景和目的造血干细胞移植（HSCT）是治疗儿童和成人恶性血液病最有效的免疫治疗策略之一。它的全球使用量一直在稳步增长。接受造血干细胞移植的患者通常需要输血支持，直到移植完成，输血需求会显著影响移植后的结果。尽管进步提高了生存率，但移植相关死亡率（TRM）仍然是实现最佳结果的主要障碍。病例介绍：我们报告一名46岁的女性，被诊断为急性髓性白血病（AML），携带FLT3-ITD突变，她接受了同种异体造血干细胞移植。供体是她的同卵双胞胎姐妹，HLA完全兼容（10/10匹配），ABO血型相同（O阳性）。值得注意的是，患者在第9天表现出快速的中性粒细胞和血小板植入，这比完全匹配的亲属或非亲属供体移植通常观察到的要早。此外，患者在移植期间不需要任何红细胞或血小板输注，也没有出现急性或慢性移植物抗宿主病（GVHD）的迹象。她在移植后三年多的时间里没有复发的迹象。结论来自同卵双胞胎供体的hsct可能提供良好的临床结果，包括在移植过程中加速植入和减少输血需求。

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引用次数: 0