Transplant immunology最新文献_第5页

Hematopoietic stem cell transplantation across ABO compatibility barrier in HLA genoidentical related donor: Is it an unfavorable factor for overall survival (OS) in Tunisian patients? 在HLA基因相同的相关供者中，跨越ABO相容性屏障的造血干细胞移植：这是突尼斯患者总生存（OS）的不利因素吗？

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-10 DOI: 10.1016/j.trim.2025.102311

Mohamed Hichem Sellami , Yesmine Boughzala , Eya Ghazouani , Nour Ben Abdeljelil , Ines Turki , Wafa Aissa , Manel Chaabane , Houda Kaabi , Tarek Ben Othman , Slama Hmida

Benchmarking of survival following Hematopoietic Stem Cell Transplantation (HSCT) is very useful in the field of transplant medicine. It has been reported that decreased survival rates after HSCT may be affected by the ABO mismatch in some cases. In this study, we aim to assess this relationship in a Tunisian cohort of adult patients who have received HSCT from HLA genoidentical related donors.

A total of 147 patients and their 147 respective related donors, were retrospectively analyzed in this study. HLA and ABO antigens typing was performed according to established routine methods. Overall Survival (OS) was measured from the date of the HSCT until death from any cause or the last follow-up examination. OS in the ABO-matched group and the ABO-mismatched groups was accessed using mean survival time, comparison of survival curves (using the Logrank test) and calculation of the hazard ratios (HR) with 95 % confidence interval (CI).

The comparison of survival curves showed no significant difference (chi2 = 0.898, p = 0.825) in the OS between the ABO-compatible graft recipients and those who are incompatible (Bidirectional, Major or Minor incompatibility). Survival analysis with HR showed no difference in mortality between the fourth targeted subgroups. This is the same result even when the source of the hematopoietic graft, i.e., peripheral blood stem cells (PBSCs) or bone marrow (BM) stem cells, was taken into consideration.

It is very likely that there is no effect of ABO mismatching on OS in Tunisian adult recipients of HSCs. This result is in good agreement with that of other recent reports that failed to establish a significant relationship between ABO incompatibility and OS after the HSCT.

造血干细胞移植（HSCT）后生存的基准测试在移植医学领域非常有用。据报道，在某些情况下，造血干细胞移植后生存率下降可能受到ABO不匹配的影响。在这项研究中，我们的目的是评估突尼斯一组接受HLA基因相同相关供者造血干细胞移植的成年患者的这种关系。本研究对147例患者及其147例相关供体进行回顾性分析。按常规方法进行HLA和ABO抗原分型。总生存期（OS）从造血干细胞移植之日起至任何原因死亡或最后一次随访检查。采用平均生存时间、生存曲线比较（采用Logrank检验）和计算风险比（HR）（95% %置信区间（CI））来获取abo匹配组和abo不匹配组的OS。生存曲线比较显示，abo血型相容与abo血型不相容（双向、主要或次要不相容）的移植受者OS无显著差异（chi2 = 0.898,p = 0.825）。HR的生存分析显示，第四个目标亚组之间的死亡率没有差异。即使考虑到造血移植物的来源，即外周血干细胞（PBSCs）或骨髓干细胞（BM），结果也是一样的。很可能ABO错配对突尼斯成年造血干细胞受者的OS没有影响。这一结果与最近其他未能建立造血干细胞移植后ABO不相容与OS之间的显著关系的报道很好地一致。

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引用次数: 0

Transplant outcomes after de novo donor specific antibody (DSA) development correlate with persistence of DSA 新供体特异性抗体（DSA）产生后的移植结果与DSA的持久性相关

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-10 DOI: 10.1016/j.trim.2025.102312

A. Jaffer , O. Shaw , D. Stringer , A. Dorling , S. Shah

Background

The OuTSMART trial confirmed de novo DSAs were associated with an increased risk of graft loss and rejection. In this post-hoc analysis, outcomes were analysed in 132 patients who had a DSA at the point of randomisation and compared between patients who had persistent DSA (DSA+/+) with those in whom the DSA was not detected on subsequent samples (DSA+/−).

Methods

Serial serum samples were collected post-enrolment until 2016. Those who had their final visit after 2018, had repeat HLA antibody testing ≥32 months post-randomisation. 115 of the 132 DSA+ patients had 2 or more samples available for analysis. 39/115 patients were persistently DSA+ and in 76/115 the DSA became undetectable at 12–32 months post enrolment.

Results

Both groups were well matched in sex, ethnicity, immunosuppression, and DSA status at transplant. The total Mean Fluorescence Intensity (MFI) of baseline DSA was significantly higher in the DSA+/+ vs DSA+/− (11,568 v 6518, P < 0.01) with a predominance of class II HLA. Significantly higher rates of antibody mediated rejection (ABMR) and death censored graft failure (GF) were seen in DSA+/+ vs in DSA+/− (15.4 % v 2.6 %, P = 0.02 and 20.5 % v 6.6 %, P = 0.03 respectively). In Cox regression analysis, persistent DSA and having both HLA classes were associated with increased risk of ABMR (HR 6.05, CI 1.2–30.0, P = 0.03 and HR 14.7, CI 1.33–162, P = 0.03 respectively). Additionally, persistent DSA was associated with higher GF rates (HR 3.4, 1.1–10.4, P = 0.03).

Conclusions

Persistent de novo DSA, after kidney transplantation, is associated with higher MFI and increased risk of ABMR and GF.

OuTSMART试验证实，新生dsa与移植物丢失和排斥反应风险增加有关。在这项事后分析中，分析了132名随机化时患有DSA的患者的结果，并比较了持续性DSA患者（DSA+/+）与后续样本中未检测到DSA的患者（DSA+/−）。方法入组后至2016年，连续采集血清样本。在2018年之后进行最后一次访问的患者，在随机分组后≥32个月重复进行HLA抗体检测。132例DSA+患者中有115例有2个或更多样本可供分析。39/115例患者持续DSA+， 76/115例患者在入组后12-32个月无法检测到DSA。结果两组患者在移植时的性别、种族、免疫抑制和DSA状态匹配良好。基线DSA的总平均荧光强度（MFI）在DSA+/+ vs DSA+/ -中显著高于（11,568 v 6518, P < 0.01），且以II类HLA为主。DSA+/+组与DSA+/ -组相比，抗体介导的排斥反应（ABMR）和死亡抑制的移植物衰竭（GF）发生率显著更高（15.4% vs 2.6%, P = 0.02和20.5% vs 6.6%, P = 0.03）。在Cox回归分析中，持续DSA和拥有两种HLA类型与ABMR风险增加相关（HR 6.05, CI 1.2-30.0, P = 0.03; HR 14.7, CI 1.33-162, P = 0.03）。此外，持续性DSA与较高的GF率相关（HR 3.4, 1.1-10.4, P = 0.03）。结论肾移植术后持续重新DSA与MFI升高、ABMR和GF风险增加相关。

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引用次数: 0

HLA-specific platelet trasfusion as part of desensitization strategy in patients with donor-specific anti-HLA antibodies before stem cell transplantation hla特异性血小板输注作为干细胞移植前供体特异性抗hla抗体患者脱敏策略的一部分。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-09 DOI: 10.1016/j.trim.2025.102310

Giuliana Lando , Roberto Crocchiolo , Giorgia Cornacchini , Giulia Di Maggio , Cristina Garanzini , Giovanni Grillo , Benedetta Mazzi , Silvano Rossini , Michela Tassara

The presence of donor-specific anti-HLA antibodies (DSAs) in patients who are candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a recognized risk factor for delayed engraftment and mortality. In the absence of an alternative donor, patient desensitization is indicated to reduce or eliminate DSAs; however, harmonization among transplant centers remains insufficient and reduction of DSAs is sometimes unsuccessful. Here, we present the feasibility and results of our recent monocenter experience on nine immunized HLA class I DSA+ patients undergoing pre-transplant desensitization using HLA-specific platelet transfusion, as a means of antibody adsorption through platelets expressing the same HLA specificities targeted by DSAs. All allo-HSCTs were from HLA-mismatched donors, both unrelated or related haploidentical. The approach appeared safe for donors and patients and potentially useful in mitigating the detrimental impact of class I DSAs, with successful engraftment observed in two of four patients with MFI > 10,000 and in all patients with MFI <10,000. Until harmonized and more risk-adapted desensitization strategies become available, sharing inter-center experiences between clinical and transfusion units will likely improve the management of hyperimmunized patients and enhance the availability of emerging desensitizing strategies.

异体造血干细胞移植（allogenic hematopoietic stem cell transplantation, alloo - hsct）的候选患者体内存在供体特异性抗hla抗体（dsa）是公认的延迟移植和死亡的危险因素。在没有替代供体的情况下，建议患者脱敏以减少或消除dsa；然而，移植中心之间的协调仍然不足，dsa的减少有时是不成功的。在这里，我们介绍了我们最近的单中心经验的可行性和结果，我们对9名免疫HLA I类DSA+患者进行移植前脱敏，使用HLA特异性血小板输注，作为一种通过表达相同HLA特异性的血小板吸附抗体的方法。所有同种异体造血干细胞均来自hla错配供体，无亲缘关系或有亲缘关系的单倍相同供体。对于供体和患者来说，该方法似乎是安全的，并且可能有助于减轻I类dsa的有害影响，在4名MFI患者中有2名 > 10,000和所有MFI患者中观察到成功的植入

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引用次数: 0

Natural killer cell KIR genotype and NKG2C phenotype in correlation to BKV infection following kidney transplantation 肾移植后自然杀伤细胞KIR基因型和NKG2C表型与BKV感染的相关性

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-06 DOI: 10.1016/j.trim.2025.102303

Shubo Tan , Xiaobin Lin , Xueqi Li, Jianhua Long, Yuan Luo, Yao Xiao, Jianjun Li

Purpose

To explore the correlation between the NK cell killer immunoglobulin-like receptor (KIR) genotype, NKG2C phenotype, and BK virus (BKV) infection following kidney transplantation.

Methods

Clinical data from 51 recipients who underwent allogeneic kidney transplantation were retrospectively analyzed. Recipients were grouped based on their KIR genotype (A/A or B/X genotype) and NKG2C⁺ NK cell ROC cut-off values. SPSS statistical analysis software was used to assess their association with BKV infection.

Results

Seventeen recipients with the KIR-A/A genotype and 34 with the KIR-B/X genotype were included in this study. Statistical analysis revealed a significant difference in the distribution of activating KIR gene numbers between the two groups. Univariate analysis revealed significant differences in survival curves between the groups according to KIR genotype and activating KIR gene number. Cox multivariate analysis identified the KIR genotype and delayed graft function as independent factors influencing BKV infection following kidney transplantation. ROC curve analysis revealed that the area under the curve for the NKG2C⁺ NK cell ratio in the infection-free survival (IFS) evaluation was 0.788, with an optimal cutoff value of 16.5 %. BKV infection rates in recipients with NKG2C⁺ NK cell ratios <16.5 % and ≥ 16.5 % were 66.7 % and 20 %, respectively. Recipients with NKG2C⁺ NK cell ratios <16.5 % had worse IFS than those with NKG2C⁺ NK cell ratios ≥16.5 %.

Conclusion

A correlation was found between NK cell KIR genotype, NKG2C⁺ NK cell phenotype, and BKV infection following kidney transplantation, providing a reference for selecting suitable donors for transplantation and reducing the risk of post-transplant BKV infection.

目的：探讨肾移植术后NK细胞杀伤免疫球蛋白样受体（KIR）基因型、NKG2C表型与BK病毒（BKV）感染的相关性。方法：回顾性分析51例异体肾移植患者的临床资料。根据受体的KIR基因型（A/A或B/X基因型）和NKG2C+ NK细胞ROC临界值对受体进行分组。采用SPSS统计分析软件评估其与BKV感染的相关性。结果：共纳入17例KIR-A/A基因型受体和34例KIR-B/X基因型受体。统计分析显示，两组之间激活KIR基因数量的分布有显著差异。单因素分析显示，根据KIR基因型和激活KIR基因数量，组间生存曲线存在显著差异。Cox多因素分析发现KIR基因型和移植延迟功能是影响肾移植后BKV感染的独立因素。ROC曲线分析显示，NKG2C+ NK细胞比例在无感染生存（IFS）评价中的曲线下面积为0.788，最佳截断值为16.5 %。NKG2C+ NK细胞比值+ NK细胞比值+ NK细胞比值≥16.5 %的受体BKV感染率。结论：NK细胞KIR基因型、NKG2C+ NK细胞表型与肾移植术后BKV感染存在相关性，为选择合适的移植供体、降低移植后BKV感染风险提供参考。

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引用次数: 0

High torque Teno virus load is associated with increased all-cause mortality risk in liver transplant recipients: a multicenter cohort study 高扭矩Teno病毒载量与肝移植受者全因死亡风险增加相关：一项多中心队列研究

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-06 DOI: 10.1016/j.trim.2025.102309

Delal Akdag , Andreas A. Rostved , Nikolai Kirkby , Allan Rasmussen , Ulrik Lassen , Claus L. Andersen , Bo-Göran Ericzon , Carl Jorns , Helena Zhao , William Bennet , Fredrik Åberg , Arno Nordin , Jens G. Hillingsø , Susanne D. Nielsen , Hans-Christian Pommergaard

Liver transplant recipients have twice the cancer risk than the general population, and de novo cancer is a leading cause of mortality after transplantation. Torque Teno Virus (TTV) is a potential marker of immune function. However, its association with long-term outcomes such as all-cause mortality and de novo cancer remains unexplored. In this Scandinavian multicenter cohort biobank study, plasma samples collected one year after transplantation were analyzed for TTV load to investigate its association with (1) all-cause mortality, (2) any de novo cancer, (3) de novo cancer excluding non-melanoma skin cancer (NMSC), and (4) NMSC using Cox regression analyses. Survival curves were plotted using Kaplan-Meier analysis. We analyzed the data of 625 liver transplant recipients. During a median follow-up of four years, 83 (13 %) recipients developed cancer (105 cancers). Of these, 39 were de novo cancers, excluding NMSC, and 66 were NMSCs. Overall, 47 recipients (8 %) died (all-cause mortality). Recipients with a high versus a low TTV load had an increased risk of all-cause mortality in the adjusted model (aHR, 5.31 [95 %CI 1.05–26.83]). The 5-year survival rates were 81 % and 100 % in the high- and low-TTV groups, respectively (p = 0.004). TTV load was not significantly associated with any de novo cancer or de novo cancer, excluding NMSC and NMSC. A high TTV load was associated with an increased risk of all-cause mortality in liver transplant recipients. With further validation, the TTV load can potentially serve as a risk stratification tool.

肝移植受者患癌症的风险是一般人群的两倍，而新发癌症是移植后死亡的主要原因。TTV （Torque Teno Virus）是一种潜在的免疫功能标志物。然而，其与全因死亡率和新发癌症等长期预后的关系仍未得到研究。在这项斯堪的纳维亚多中心队列生物库研究中，对移植后一年收集的血浆样本进行TTV负荷分析，以调查其与(1)全因死亡率、(2)任何新生癌症、(3)除非黑色素瘤皮肤癌（NMSC）外的新生癌症以及(4)NMSC之间的关系。采用Kaplan-Meier分析绘制生存曲线。我们分析了625例肝移植受者的资料。在中位随访4年期间，83名（13. %）受者患癌（105例）。其中39例为新发癌症，不包括NMSC， 66例为NMSC。总体而言，47名受者（8 %）死亡（全因死亡率）。在调整后的模型中，高TTV负荷与低TTV负荷的受者全因死亡风险增加（aHR, 5.31[95 %CI 1.05-26.83]）。高ttv组和低ttv组的5年生存率分别为81 %和100 % （p = 0.004）。除NMSC和NMSC外，TTV负荷与任何新发癌症或新发癌症均无显著相关性。高TTV负荷与肝移植受者全因死亡风险增加有关。通过进一步的验证，TTV负荷可以作为潜在的风险分层工具。

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引用次数: 0

CXCL11 as potential predictive biomarker and therapeutic target of acute rejection after kidney transplantation CXCL11作为肾移植后急性排斥反应的潜在预测生物标志物和治疗靶点。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-05 DOI: 10.1016/j.trim.2025.102306

Jie Zhang, Chengjun Yu, Huyu Wang, Hanyu Xiao, Sheng Wen, Yi Hua, Guanghui Wei

Kidney transplantation is the optimal treatment method for chronic kidney disease. Although the short-term and long-term survival rates of transplanted kidneys have been significantly improved with the development of immunosuppressive agents, acute rejection remains the main risk factor threatening the survival of the allografts and patient. We utilized bioinformatics analysis to identify the predictive and therapeutic target of acute rejection after kidney transplantation. In the results, cytokines were considered as critical role in allografts acute rejection, and most cytokines were increased in the process of AR. According to the machine learning algorithm analysis and receiver operating characteristic curve results, CXCL11 was identified as the most valued cytokine in prediction of AR. Single-gene GSEA results showed CXCL11 was strongly associated with AR-related biological behavior. Subsequent analysis results showed the gene RELA regulate the expression of CXCL11 and mainly distribute in renal tubular epithelial cells. In cell experiments, LPS as the activator of NF-κB signaling pathway induced the expression of CXCL11. In animal experiments, compared to syn group, severe acute rejection occurs in allo group, and companied with severe inflammatory reaction and the expression of CXCL11, as the activation of NF-κB signaling pathway. CXCR3 specifically recognizes CXCL11 as one of its ligands, single cell analysis demonstrated CXCR3 and CD8 were co-expression on the T cells in the microenvironment of allografts. Finally, we demonstrated in allo group of rat kidney transplantation, there were a large number of CXCR3 + CD8+ T cells infiltrated the allografts. Conclusion, we utilized bioinformatics analysis tools, finally identified CXCL11 as the potential target for prediction and treatment in acute rejection after kidney transplantation.

肾移植是慢性肾脏疾病的最佳治疗方法。尽管随着免疫抑制剂的发展，移植肾脏的短期和长期存活率显著提高，但急性排斥反应仍然是威胁同种异体移植物和患者生存的主要危险因素。我们利用生物信息学分析来确定肾移植后急性排斥反应的预测和治疗靶点。结果表明，细胞因子在同种异体移植物急性排斥反应中起着至关重要的作用，大多数细胞因子在AR过程中升高。根据机器学习算法分析和受体工作特征曲线结果，CXCL11被确定为预测AR最有价值的细胞因子。单基因GSEA结果显示CXCL11与AR相关的生物学行为密切相关。随后的分析结果显示RELA基因调控CXCL11的表达，主要分布在肾小管上皮细胞中。在细胞实验中，LPS作为NF-κB信号通路的激活剂诱导CXCL11的表达。在动物实验中，与syn组相比，同种异体组出现严重的急性排斥反应，并伴有严重的炎症反应和CXCL11的表达，这是由于NF-κB信号通路的激活。CXCR3特异性识别CXCL11作为其配体之一，单细胞分析表明CXCR3和CD8在同种异体移植物微环境下的T细胞上共表达。最后，我们证明在大鼠肾移植同种异体组中，有大量的CXCR3 + CD8+ T细胞浸润同种异体移植物。结论利用生物信息学分析工具，最终确定了CXCL11作为预测和治疗肾移植急性排斥反应的潜在靶点。

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引用次数: 0

Diagnostic value of dd-cfDNA and CXCL-10 in kidney allograft recipients for identifying acute rejection dd-cfDNA和CXCL-10对肾移植受者急性排斥反应的诊断价值。

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-05 DOI: 10.1016/j.trim.2025.102307

Qi Yu , Yan Zhang , Zijian Gao , Boqian Wang , Hongwei Yang , Long He

Background and hypothesis

Acute rejection (AR) remains a major challenge in kidney transplantation. Current methods used to diagnose acute rejection are either invasive or not sufficiently sensitive. Thus, in this study, we aimed to develop a novel and sensitive diagnostic tool for predicting acute rejection after kidney transplantation. We investigated if donor-derived cell-free DNA (dd-cfDNA) in the serum and C-X-C motif chemokine 10 (CXCL-10) levels were closely related to the occurrence of AR after renal transplantation.

Methods

We collected data and tested the serum levels of dd-cfDNA and CXCL-10 in AR patients and patients who underwent kidney transplantation during the same period. Logistic analysis was used to verify risk factors associated with AR. The analysis of the receiver operating characteristic curve(ROC) was used to reveal correlation between dd-cfDNA，CXCL-10 levels and AR patients.

Results

We included 13 AR patients and 18 patients without acute rejection. The AR group had a lower BMI (P = 0.006), and higher levels of eGFR (P = 0.006) and CysC (P = 0.009). Additionally, ln dd-cfDNA percentage and ln CXCL-10 content were higher in the AR group compared to the control group (P = 0.007, P = 0.004).The results of logistic analysis suggested CysC(OR:2.562[95 % CI:1.377–4.766]，P = 0.003),ln dd-cfDNA percent (OR: 10.521 [95 % CI: 2.091–52.938]，P = 0.004), and ln CXCL-10 content(OR:49.052 [95 % CI: 1.730–1391.073]，P = 0.023) can indicate the risk of AR and were independently correlated with the occurrence of acute rejection of the kidney graft. The AUC of serum dd-cfDNA (AUC = 0.723, P = 0.0348) percent and CXCL-10 content (AUC = 0.814, P = 0.0029) showed significant diagnostic performance. The combined dd-cfDNA and CXCL-10 diagnosis showed higher AUC and specificity.

Conclusions

Serum dd-cfDNA and CXCL-10 levels were significantly elevated in patients with acute rejection. Thus, dd-cfDNA and CXCL-10 can play suggestive roles in detecting graft injury after kidney transplantation.

背景和假设：急性排斥反应（AR）仍然是肾移植的主要挑战。目前用于诊断急性排斥反应的方法要么是侵入性的，要么不够敏感。因此，在这项研究中，我们旨在开发一种新的、灵敏的诊断工具来预测肾移植后的急性排斥反应。我们研究了血清中供体来源的无细胞DNA （dd-cfDNA）和C-X-C基序趋化因子10 （CXCL-10）水平是否与肾移植后AR的发生密切相关。方法：收集资料，检测AR患者和同期肾移植患者血清中dd-cfDNA和CXCL-10水平。采用Logistic分析验证与AR相关的危险因素。采用受试者工作特征曲线（receiver operating characteristic curve， ROC）分析dd-cfDNA、CXCL-10水平与AR患者的相关性。结果：我们纳入13例AR患者和18例无急性排斥反应的患者。AR组BMI较低（P = 0.006），eGFR （P = 0.006）和CysC （P = 0.009）水平较高。此外，AR组的ln dd-cfDNA百分比和ln CXCL-10含量高于对照组（P = 0.007,P = 0.004）。物流分析的结果提出CysC (OR: 2.562(95 %置信区间:1.377—-4.766),P = 0.003),ln dd-cfDNA百分比(OR: 10.521(95 %置信区间:2.091—-52.938),P = 0.004),和ln CXCL-10内容(OR: 49.052(95 %置信区间:1.730—-1391.073),P = 0.023)可以表明基于“增大化现实”技术的风险,独立与肾移植急性排斥反应的发生。血清dd-cfDNA的AUC (AUC = 0.723,P = 0.0348)%和CXCL-10含量（AUC = 0.814,P = 0.0029）具有显著的诊断价值。dd-cfDNA和CXCL-10联合诊断显示更高的AUC和特异性。结论：急性排斥反应患者血清dd-cfDNA和CXCL-10水平显著升高。因此，dd-cfDNA和CXCL-10在肾移植后移植物损伤检测中具有提示作用。

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引用次数: 0

WITHDRAWN: Pretreatment hemoglobin, myeloma subtype, and induction regimens as independent prognostic factors for survival after autologous stem cell transplantation in multiple myeloma: A retrospective cohort study 预处理血红蛋白、骨髓瘤亚型和诱导方案作为多发性骨髓瘤患者自体干细胞移植后生存的独立预后因素：一项回顾性队列研究

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-05 DOI: 10.1016/j.trim.2025.102305

Yong Zhang, Guangzhong Yang, Wen Gao, Wenming Chen

This article has been withdrawn at the request of the author(s) and/or editor due to an error in the publishing process. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal

背景：自体造血干细胞移植（auto-HSCT）是符合条件的多发性骨髓瘤（MM）患者的标准治疗。然而，结果差异很大。虽然细胞遗传学和国际分期系统（ISS）是确定的预后标志物，但预处理血红蛋白（Hb）水平、骨髓瘤亚型和特异性诱导方案的独立预测作用仍不明确。本研究旨在评估这些因素，以完善风险分层和改善预后。方法：我们回顾性分析了2001年至2019年在北京朝阳医院接受首次自体造血干细胞移植的350例MM患者。我们评估了基线变量对预后的影响，包括Hb水平（结果：中位随访时间为58 个月）。整个队列的中位PFS和OS分别为42 个月（95 % CI 36-48）和98 个月（95 % CI 83-113）。基线Hb水平与骨髓浆细胞浸润呈负相关（r = -0.45,P ）结论：本研究确定预处理血红蛋白、IgG亚型和硼替佐米诱导是MM患者自体造血干细胞移植后生存结果的重要且独立的预测因素。我们的研究结果强调了基线血红蛋白的预后作用，这是一种简单且普遍可用的标志物，可反映肿瘤负荷和肾功能，补充了既定的风险因素，如ISS分期和细胞遗传学。这些结果支持将这些因素整合到预后模型中，以更好地定制治疗策略和管理患者期望。

引用次数: 0

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 : 2025-10-04 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

Macrophage activation via the NTPDase1-adenosine pathway and associated injury in acute antibody-mediated rejection 急性抗体介导的排斥反应中巨噬细胞通过ntpdase1 -腺苷途径激活和相关损伤

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology

Pub Date : 2025-10-04 DOI: 10.1016/j.trim.2025.102302

Pu Yan , Yong Zhang , Zhongbao Zhou , Yongjin Huang , Peng Xue , Xiaoyan Wang

Background

Nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) is a calcium- and magnesium-dependent nucleoside triphosphate diphosphohydrolase. NTPDase1, expressed in mature immune cells to hydrolyze ATP and ADP into adenosine. The NTPDase1and its function in an adenosine pathway plays an important role in suppressing inflammation, immune responses, cell proliferation, and other processes. We investigated the effects and mechanisms of macrophage activation through the NTPDase1-adenosine pathway and the resulting damage from acute antibody-mediated rejection (AMR).

Methods

We established an acute AMR skin-graft model by transplanting MHC-mismatched B10.A ear skin onto BALB/c nude mice and inducing rejection with 100 μg anti-H-2Kk IgG. Mice were grouped as wild-type, NTPDase1-knockout, and NTPDase1-overexpression, with isotype-IgG controls. Outcomes were compared across groups, and statistical analyses were performed using SPSS 16.0.

Results

After the onset of acute AMR, higher NTPDase1 expression in B cells and grafted skin was associated with lower concentration of extracellular ADP, a reduced proportion of CD68+ macrophages, and milder pathological injury in nude mice, and each parameter showing a negative correlation. At 30 min after AMR onset, CD68 + TNF-α + M1 macrophages predominated, whereas CD68 + CD163+ M2 macrophage numbers did not change significantly. Over time, M1 macrophages progressively decreased, and M2 macrophages became increasingly prominent. By day 7 after AMR onset, compared with controls, CD163+ M2 macrophages and the expression of TGF-β1, vimentin, and α-SMA were significantly increased, whereas the epithelial marker E-cadherin was significantly decreased.

Conclusion

NTPDase1 constrains acute AMR by limiting extracellular ADP, curbing macrophage expansion, and reducing graft injury. Transgenic overexpression sustained expression, moderated M1-to-M2 dynamics, and attenuated C4d and fibrotic markers, whereas knockout intensified purinergic signaling, inflammation, and fibrosis. Findings position NTPDase1 as a protective regulator and therapeutic target in AMR.

背景：核苷三磷酸二磷酸水解酶1 （NTPDase1）是一种钙镁依赖性核苷三磷酸二磷酸水解酶。NTPDase1，在成熟免疫细胞中表达，将ATP和ADP水解成腺苷。ntpdase1及其在腺苷途径中的功能在抑制炎症、免疫反应、细胞增殖等过程中发挥重要作用。我们研究了通过ntpdase1 -腺苷途径激活巨噬细胞的作用和机制，以及急性抗体介导的排斥反应（AMR）造成的损伤。方法：通过移植mhc错配的B10建立急性AMR皮肤移植模型。BALB/c裸鼠耳皮，100 μg抗h - 2kk IgG诱导排斥反应。将小鼠分为野生型、ntpdase1敲除型和ntpdase1过表达型，并以同型igg为对照。各组结果比较，采用SPSS 16.0进行统计学分析。结果：急性AMR发生后，裸鼠B细胞和移植皮肤NTPDase1表达升高与细胞外ADP浓度降低、CD68+巨噬细胞比例降低、病理损伤减轻相关，且各参数呈负相关。在AMR发生30 min后，CD68 + TNF-α + M1巨噬细胞数量占主导地位，而CD68 + CD163+ M2巨噬细胞数量无显著变化。随着时间的推移，M1巨噬细胞逐渐减少，M2巨噬细胞日益突出。AMR发生后第7天，与对照组相比，CD163+ M2巨噬细胞及TGF-β1、vimentin、α-SMA的表达显著升高，上皮标志物E-cadherin的表达显著降低。结论：ntpdese1通过限制细胞外ADP、抑制巨噬细胞扩张、减轻移植物损伤来抑制急性AMR。转基因过表达持续表达，减缓m1到m2的动态，减弱C4d和纤维化标志物，而敲除嘌呤能信号，炎症和纤维化。研究结果表明，NTPDase1是AMR的保护调节因子和治疗靶点。

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引用次数: 0