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Recovery of CMV immunity after allogeneic haematopoietic stem cell transplant — Insight from an in-depth analysis of a small cohort of patients with clinical correlation 同种异体造血干细胞移植后巨细胞病毒免疫的恢复——对具有临床相关性的小队列患者的深入分析
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.trim.2026.102344
Yeh-ching Linn, Kirubavathy Sundar Raj

Background

We conducted an evaluation of the IFN-g ELISpot assay with the primary objective of exploring its clinical use after allogeneic haematopoietic stem cell transplant (allo-HSCT). Here we analysed its correlation with occurrence of clinically-significant CMV infection (cs-CMVi) and risk factors.

Method

Frozen mononuclear cells collected at 2, 3, 4 and 5 months after allo-HSCT were tested against CMV pooled peptide pp65 and IE1 in an IFN-g ELISpot assay. Spot forming cells (SFC) per 250,000 cells were correlated with clinical course.

Results

Amongst the 18 CMV seropositive recipients including 3 with seronegative donors, 11 of the 14 low responders (< 50 SFC) developed cs-CMVi while all the 4 high responders with >50 SFC were protected. High dose glucocorticoids (1 mg/kg or higher) predisposed to a second episode of cs-CMVi even after acquisition of more than 50 SFC after the first episode, while low dose (20 mg/day or lower) did not matter. Low level CMV viremia resolved spontaneously in 2 of the 4 high responders but progressed to cs-CMVi in the other 11 low responders. Consistent with literature, recipients of T-depleting regimen and cord blood were at a higher risk of cs-CMVi. The median time to first acquisition of more than 50 SFC was 118 days. The 3 recipients of seronegative donors did not recover immunity beyond the monitoring period and 2 had recurrent cs-CMVi.

Conclusion

This small series provides in-depth insight into the recovery of CMV immunity and cs-CMVi post allo-HSCT for each recipient and supplements knowledge provided by large series.
背景:我们对IFN-g ELISpot检测进行了评估,主要目的是探索其在同种异体造血干细胞移植(alloo - hsct)后的临床应用。在这里,我们分析了其与临床显著巨细胞病毒感染(cs-CMVi)的发生和危险因素的相关性。方法:采用IFN-g ELISpot法检测同种异体造血干细胞移植后2、3、4和5 个月收集的冷冻单核细胞对CMV合并肽pp65和IE1的抑制作用。每25万个细胞中斑点形成细胞(SFC)与临床病程相关。结果:18例CMV血清阳性受者(3例血清阴性供者)中,14例低应答者(< 50 SFC)中有11例发展为cs-CMVi,而4例高应答者(< 50 SFC)均得到保护。高剂量糖皮质激素(1 mg/kg或更高)即使在首次发作后获得超过50 SFC后也易导致cs-CMVi第二次发作,而低剂量(20 mg/天或更低)则无关紧要。在4例高应答者中,2例低水平CMV病毒血症自发消退,但在其他11例低应答者中进展为cs-CMVi。与文献一致,接受t消耗方案和脐带血的患者cs-CMVi的风险更高。首次收购超过50家SFC的中位数时间为118 天。3例血清阴性供体受者在监测期后未恢复免疫力,2例复发。结论:这个小系列深入了解了每个受体在同种异体造血干细胞移植后CMV免疫和cs-CMVi的恢复情况,并补充了大系列提供的知识。
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引用次数: 0
TLR3 stimulation rejuvenates aged mesenchymal stem cells and restores immunosuppressive function in graft-versus-host disease TLR3刺激使衰老的间充质干细胞恢复活力,并恢复移植物抗宿主病的免疫抑制功能。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.trim.2026.102346
Linlin Jin , Ziqi Hu , Yuxin Huang , Haihui Xu , Nuo Li , Aoli Zhang , Yongjuan Duan , Peng Wu , Shuhai Lan , Jiarui Zheng , Tianyuan Hu , Yingchi Zhang
Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation, particularly in patients who are refractory to corticosteroids. Mesenchymal stem cells (MSCs) possess immunosuppressive properties and are being explored as a treatment for GVHD. However, their therapeutic efficacy declines with extensive in vitro expansion due to cellular aging. Therefore, this study aimed to investigate the effects of MSC aging on GVHD outcomes and explore strategies to rejuvenate aged MSCs. Specifically, we compared the therapeutic efficacies of early (P5) and late passage (P15) human MSCs in a murine model of GVHD. Single-cell RNA sequencing was performed to identify molecular alterations associated with MSC aging. Polyinosinic:polycytidylic acid [poly(I:C)], a Toll-like receptor 3 (TLR3) agonist, was used to stimulate aged MSCs. Early passage MSCs significantly alleviated the severity of GVHD, improved survival, and reduced systemic inflammation (p < 0.05). In contrast, late-passage MSCs showed minimal therapeutic effect. Single-cell transcriptomics revealed that MSC aging is associated with the loss of immunoregulatory subpopulations and downregulation of TLR3 signaling. Notably, poly(I:C) priming partially reversed the senescence phenotypes and restored the immunosuppressive capacity of aged MSCs, resulting in enhanced suppression of T cell proliferation, increased T cell apoptosis and G1 accumulation, and reduced IFN-related readouts (p < 0.05).Mechanistically, replicative senescence impairs the immunoregulatory potency of MSCs by disrupting TLR3-mediated signaling pathways. Overall, TLR3 activation by poly(I:C) rejuvenates aged MSCs and restores their therapeutic function, providing a clinically translatable strategy for enhancing MSC-based immunotherapies for GVHD.
移植物抗宿主病(GVHD)仍然是异体造血干细胞移植的主要并发症,特别是在对皮质类固醇难治的患者中。间充质干细胞(MSCs)具有免疫抑制特性,正在被探索作为GVHD的治疗方法。然而,由于细胞老化,它们的治疗效果随着体外扩展而下降。因此,本研究旨在研究MSC衰老对GVHD结果的影响,并探索使衰老MSCs恢复活力的策略。具体来说,我们比较了早期(P5)和晚期(P15)人间充质干细胞在GVHD小鼠模型中的治疗效果。进行单细胞RNA测序以鉴定与MSC衰老相关的分子改变。polyinosic:polycytidylic acid [poly(I:C)]是toll样受体3 (TLR3)激动剂,用于刺激衰老的MSCs。早期传代MSCs可显著减轻GVHD的严重程度,提高生存率,并减少全身炎症(p
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引用次数: 0
CD34+/CD3+ cells ratio in the peripheral blood stem cells product and graft-versus-host disease: Is there still room for improvement? 外周血干细胞产物中的CD34+/CD3+细胞比例和移植物抗宿主病:还有改进的空间吗?
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.trim.2026.102347
Ewa Bembnista , Paula Matuszak , Anna Łojko-Dankowska , Dominik Dytfeld , Magdalena Matuszak , Anna Wache , Katarzyna Kaźmierska , Andrzej Szczepaniak , Bartosz Małecki , Patrycja Stawicka , Joanna Kujawska , Anna Płotka , Anna Hoppe , Justyna Marcinkowska , Kinga Eling , Krzysztof Lewandowski , Lidia Gil
Allogeneic hematopoietic stem cell (allo-HSC) transplantation (allo-HSCT) is a therapy of choice for patients requiring total bone marrow replacement. One of the critical issues is optimizing the number of allo-HSCs for successful outcomes, measured by the engraftment time and the incidence/severity of graft versus host disease (GvHD). We evaluated engraftment time and GvHD in comparison to the composition of infused CD34+ immature HSCs and CD3+ T cells in all-HSCTs. The study evaluated 97 patients with allo-HSCT from matched related (group MRD; n = 40), matched unrelated (group MUD; n = 28), mismatched unrelated (group MMUD; n = 6), and haploidentical (group haplo; n = 23) donors. Overall, we did not observe any correlation between the total count of CD34+ allo-HSC and CD3+ T cells or the count of CD34+ and CD3+ calculated per kilogram of body weight (kg) on engraftment as well as GvHD symptoms in all studied groups. However, the CD34+/CD3+ ratio may provide valuable information in the process of a graft quality assessment in haploidentical allo-HCST for the choice of therapeutic options.
同种异体造血干细胞(alloo - hsc)移植(alloo - hsct)是需要全骨髓置换的患者的治疗选择。其中一个关键问题是通过移植时间和移植物抗宿主病(GvHD)的发生率/严重程度来优化同种造血干细胞的数量,以获得成功的结果。我们评估了移植时间和GvHD,比较了所有hsct中注入的CD34+未成熟hsc和CD3+ T细胞的组成。该研究评估了来自匹配亲属(MRD组,n = 40)、匹配非亲属(MUD组,n = 28)、不匹配非亲属(MMUD组,n = 6)和单倍体(haplo组,n = 23)供体的97例同种异体造血干细胞移植患者。总的来说,在所有研究组中,我们没有观察到CD34+同种异体hsc和CD3+ T细胞的总数或移植时每公斤体重计算的CD34+和CD3+计数与GvHD症状之间的任何相关性。然而,CD34+/CD3+比值在评估同种异体hcst移植质量的过程中可能为选择治疗方案提供有价值的信息。
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引用次数: 0
Novel, short-course, low-dose total lymphoid irradiation (TLI) post heart transplant for recalcitrant rejection – A single centre experience 新型、短疗程、低剂量全淋巴细胞照射(TLI)治疗心脏移植后顽固性排斥反应-单中心经验。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI: 10.1016/j.trim.2025.102333
Felicity Lee , B.N. Clare Fazackerley , Tee S. Lim , Lloyd D'Orsogna , Jon Downing , Linh Truong , Amit Shah , Jay Baumwol , Kaitlyn Lam , James Lambert , Peter Dias , Faith Njue , Lawrence Dembo

Background

A previous small study (2007) of patients who received short-course, low-dose total lymphoid irradiation (sTLI) as treatment for recalcitrant cardiac rejection post-heart transplantation (HTx) reported good treatment compliance without significant toxicities and improvement in rejection frequency. We conducted a retrospective analysis, evaluating longer-term outcomes in this patient cohort.

Methods and results

We reviewed the medical records of 21 HTx recipients (mean age ± std. 43.7 ± 12.8 years; 47.6 % female) who received sTLI between 2001 and 2023. Five patients were highly sensitized pre-HTx (calculated panel-reactive antibody >80 %) and 8 patients received induction immunosuppression at time of HTx. Patients received 4.5Gy in four fractions over 4 consecutive days administered (n = 13 as an outpatient), at a median of 442 (IQR 47–966) days post-HTx. STLI was well-tolerated symptomatically with no persistent lymphopenias. Eleven patients had no further rejection. Ten patients had immediate rejection resolution with later rejection detected (median 401 [IQR 301–1569] days post-sTLI). Thirteen patients, mostly transplanted pre-2010, have deceased (median graft survival 7.6 years, mean follow-up 9.4 years). One patient died of metastatic colon cancer. There were no haematological malignancies. Two patients received a second sTLI course and subsequent re-HTx.

Conclusions

We report the largest case series of patients who received sTLI post-HTx. STLI is well-tolerated, with resolution of immediate recalcitrant rejection in all patients and resolution of rejection in the longer term in 52 %. STLI is a possible alternative option for patients with cardiac rejection refractory to routine, augmented immunotherapy. Further larger studies are required to assess the longer-term efficacy and safety of this treatment.
背景:之前的一项小型研究(2007年)对接受短疗程、低剂量全淋巴细胞照射(sTLI)治疗心脏移植后顽固性心脏排斥反应(HTx)的患者进行了研究,报告了良好的治疗依从性,没有明显的毒性和排斥反应频率的改善。我们进行了回顾性分析,评估该患者队列的长期结果。方法与结果:我们回顾了21例HTx受者(平均年龄 ± )的病历。 43.7±12.8  年;47.6 %女性),在2001年至2023年间接受sTLI治疗。5例患者在HTx前高度致敏(计算出面板反应抗体>80 %),8例患者在HTx时接受诱导免疫抑制。患者在连续4天内分四部分接受4.5Gy (n = 13,作为门诊患者),htx后中位数为442 (IQR 47-966)天。STLI在症状上耐受良好,无持续性淋巴细胞减少。11名患者没有出现进一步的排斥反应。10例患者即刻排异反应消退,随后发现排异反应(stli后中位401 [IQR 301-1569]天)。13例患者,大多数在2010年前移植,已经死亡(中位移植生存7.6 年,平均随访9.4 年)。一名患者死于转移性结肠癌。无血液学恶性肿瘤。两名患者接受了第二次sTLI治疗,随后再次接受htx治疗。结论:我们报道了htx术后接受sTLI的最大病例系列。STLI耐受性良好,所有患者立即出现顽固性排斥反应,52% %的患者长期出现排斥反应。STLI是对常规增强免疫治疗难治性心脏排斥患者的一种可能的替代选择。需要更大规模的研究来评估这种治疗的长期疗效和安全性。
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引用次数: 0
Conversion to belatacept-based immunosuppression as a calcineurin sparing regimen in lung transplant: A multi-institutional retrospective study 在肺移植中转换为基于belataccept的免疫抑制作为钙调磷酸酶保留方案:一项多机构回顾性研究。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI: 10.1016/j.trim.2025.102330
Moustafa Younis , Cecelia M. Miller , Christopher I. Mederos , Ariana Ishaq , Pooja Kumar , Biplab Saha , Cynthia Gries , Victoria Reams , Vaidehi Kaza , Srinivas Bollineni , Fernando Torres , Mohammad A. Aladaileh , Mindaugas Rackauskas , Irina Timofte , Amir Emtiazjoo

Background

Calcineurin inhibitor (CNI) related kidney dysfunction is common and associated with worse outcomes after lung transplantation (LTx). To mitigate that risk, belatacept use in a CNI-sparing regimen is an alternative in LTx. We aim to describe our experience using belatacept as a CNI-sparing regimen in LTx.

Methods

A multi-institutional retrospective review of LTx patients who received belatacept (1/2018–8/2023) was performed. The primary outcome is the change in estimated glomerular filtration rate (eGFR) after initiation of belatacept. Secondary outcomes were compared with a control group of patients transplanted during 1/2018–8/2023 that did not receive belatacept. Secondary outcomes include acute cellular rejection (ACR), denovo donor specific antibodies (DSA), antibody mediated rejection (AMR), infections, malignancy, chronic lung allograft dysfunction (CLAD) and mortality.

Results

A total of 170 LTx patients who received belatacept were included for the primary outcome. To investigate the secondary outcomes an additional 288 LTx controls were used. The median (IQR) eGFR at the time of belatacept initiation, six months, and one year post belatacept initiation was 43 (34–52), 46 (37–53) and 43 (36–53) mL/min/1.73 m2, respectively (p = 0.21). There was no significant difference in ACR, DSA, AMR, infections, malignancy, CLAD or mortality between both groups.

Conclusions

Belatacept CNI-sparing therapy was well tolerated and feasible in LTx recipients, with renal function appearing to stabilize over time and no apparent safety signal for acute rejection, infection, malignancy, CLAD, or mortality.
背景:钙调磷酸酶抑制剂(CNI)相关的肾功能障碍是常见的,并且与肺移植(LTx)后较差的预后相关。为了减轻这种风险,在LTx中,在cni保留方案中使用belataccept是一种替代方案。我们的目的是描述我们在LTx中使用belataccept作为cni保护方案的经验。方法:对接受belataccept治疗的LTx患者(2018年1月- 2023年8月)进行多机构回顾性分析。主要结局是开始服用后估计肾小球滤过率(eGFR)的变化。次要结果与2018年1月至2023年8月期间未接受belataccept的移植患者的对照组进行比较。次要结局包括急性细胞排斥反应(ACR)、首发供体特异性抗体(DSA)、抗体介导的排斥反应(AMR)、感染、恶性肿瘤、慢性同种异体肺功能障碍(CLAD)和死亡率。结果:共有170例LTx患者接受了belataccept纳入主要结局。为了调查次要结果,另外使用了288例LTx对照。belatacept起始时、起始后6个月和1年的中位(IQR) eGFR分别为43(34-52)、46(37-53)和43 (36-53)mL/min/1.73 m2 (p = 0.21)。两组间ACR、DSA、AMR、感染、恶性、覆层及死亡率无显著差异。结论:在LTx受者中,Belatacept保留cni治疗耐受性良好且可行,肾功能随着时间的推移趋于稳定,并且没有明显的排斥反应、感染、恶性肿瘤、CLAD或死亡率的安全信号。
{"title":"Conversion to belatacept-based immunosuppression as a calcineurin sparing regimen in lung transplant: A multi-institutional retrospective study","authors":"Moustafa Younis ,&nbsp;Cecelia M. Miller ,&nbsp;Christopher I. Mederos ,&nbsp;Ariana Ishaq ,&nbsp;Pooja Kumar ,&nbsp;Biplab Saha ,&nbsp;Cynthia Gries ,&nbsp;Victoria Reams ,&nbsp;Vaidehi Kaza ,&nbsp;Srinivas Bollineni ,&nbsp;Fernando Torres ,&nbsp;Mohammad A. Aladaileh ,&nbsp;Mindaugas Rackauskas ,&nbsp;Irina Timofte ,&nbsp;Amir Emtiazjoo","doi":"10.1016/j.trim.2025.102330","DOIUrl":"10.1016/j.trim.2025.102330","url":null,"abstract":"<div><h3>Background</h3><div>Calcineurin inhibitor (CNI) related kidney dysfunction is common and associated with worse outcomes after lung transplantation (LTx). To mitigate that risk, belatacept use in a CNI-sparing regimen is an alternative in LTx. We aim to describe our experience using belatacept as a CNI-sparing regimen in LTx.</div></div><div><h3>Methods</h3><div>A multi-institutional retrospective review of LTx patients who received belatacept (1/2018–8/2023) was performed. The primary outcome is the change in estimated glomerular filtration rate (eGFR) after initiation of belatacept. Secondary outcomes were compared with a control group of patients transplanted during 1/2018–8/2023 that did not receive belatacept. Secondary outcomes include acute cellular rejection (ACR), denovo donor specific antibodies (DSA), antibody mediated rejection (AMR), infections, malignancy, chronic lung allograft dysfunction (CLAD) and mortality.</div></div><div><h3>Results</h3><div>A total of 170 LTx patients who received belatacept were included for the primary outcome. To investigate the secondary outcomes an additional 288 LTx controls were used. The median (IQR) eGFR at the time of belatacept initiation, six months, and one year post belatacept initiation was 43 (34–52), 46 (37–53) and 43 (36–53) mL/min/1.73 m2, respectively (<em>p</em> = 0.21). There was no significant difference in ACR, DSA, AMR, infections, malignancy, CLAD or mortality between both groups.</div></div><div><h3>Conclusions</h3><div>Belatacept CNI-sparing therapy was well tolerated and feasible in LTx recipients, with renal function appearing to stabilize over time and no apparent safety signal for acute rejection, infection, malignancy, CLAD, or mortality.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102330"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655446","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
Impact of everolimus-based immunosuppression on transplant rejection or death in lung transplant recipients using the United States Food and Drug Administration Adverse Event Reporting System 依维莫司为基础的免疫抑制对肺移植受者移植排斥或死亡的影响使用美国食品和药物管理局不良事件报告系统
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.trim.2026.102345
Toru Ogura , Chihiro Shiraishi , Aiko Urawa

Background

The off-label use of everolimus in lung transplant recipients (LTRs) has increased; however, its safety profile across different immunosuppressive regimens remains insufficiently characterized. This study explored potential safety signals associated with the addition of everolimus to established immunosuppressive regimens using real-world data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods

A retrospective observational analysis of FAERS data was conducted. To reduce potential confounding from drug–drug interactions, paired comparisons were restricted to regimen pairs that differed only by the presence or absence of everolimus. Reporting odds ratios (RORs) and adjusted RORs (aRORs) were calculated for each regimen, using the corresponding non-everolimus regimen as the reference. Associations were examined for the composite outcome of transplant rejection or death.

Results

The everolimus plus tacrolimus regimen showed lower reporting of the composite outcome compared with the tacrolimus regimen (ROR: 0.238 [95% confidence interval (CI): 0.073–0.782], p = 0.018; aROR: 0.258 [95% CI: 0.078–0.860], p = 0.027). For other regimens, including tacrolimus plus prednisone, cyclosporine, and cyclosporine plus prednisone plus mycophenolate mofetil, the addition of everolimus showed a consistent but non-significant trend toward lower reporting (all RORs <1 and aRORs <1).

Conclusions

Analysis of FAERS data identified a potential signal of lower reporting of transplant rejection or death associated with the addition of everolimus to certain immunosuppressive regimens in LTRs. These findings warrant cautious interpretation because of the inherent limitations of FAERS and require validation in prospective studies.
背景:依维莫司在肺移植受者(LTRs)中的超说明书使用有所增加;然而,其安全性在不同的免疫抑制方案中仍未充分表征。本研究利用来自美国食品和药物管理局不良事件报告系统(FAERS)的真实数据,探讨了在已建立的免疫抑制方案中加入依维莫司的潜在安全信号。方法:回顾性观察分析FAERS资料。为了减少药物-药物相互作用的潜在混淆,配对比较仅限于仅因有无依维莫司而不同的方案对。以相应的非依维莫司方案为参考,计算每个方案的报告优势比(RORs)和调整后的优势比(aRORs)。研究了移植排斥反应或死亡的复合结果的相关性。结果:依维莫司联合他克莫司方案与他克莫司方案相比,复合结局的报告率较低(ROR: 0.238[95%可信区间(CI): 0.073-0.782], p = 0.018;aROR: 0.258 [95% CI: 0.078 ~ 0.860], p = 0.027)。对于其他方案,包括他克莫司加泼尼松、环孢素和环孢素加泼尼松加霉酚酸酯,加入依维莫司显示出一致但不显著的低报告趋势(所有RORs)。结论:FAERS数据分析发现,在LTRs中,在某些免疫抑制方案中加入依维莫司可能会降低移植排斥反应或死亡报告。由于FAERS的固有局限性,这些发现需要谨慎解释,并需要在前瞻性研究中进行验证。
{"title":"Impact of everolimus-based immunosuppression on transplant rejection or death in lung transplant recipients using the United States Food and Drug Administration Adverse Event Reporting System","authors":"Toru Ogura ,&nbsp;Chihiro Shiraishi ,&nbsp;Aiko Urawa","doi":"10.1016/j.trim.2026.102345","DOIUrl":"10.1016/j.trim.2026.102345","url":null,"abstract":"<div><h3>Background</h3><div>The off-label use of everolimus in lung transplant recipients (LTRs) has increased; however, its safety profile across different immunosuppressive regimens remains insufficiently characterized. This study explored potential safety signals associated with the addition of everolimus to established immunosuppressive regimens using real-world data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).</div></div><div><h3>Methods</h3><div>A retrospective observational analysis of FAERS data was conducted. To reduce potential confounding from drug–drug interactions, paired comparisons were restricted to regimen pairs that differed only by the presence or absence of everolimus. Reporting odds ratios (RORs) and adjusted RORs (aRORs) were calculated for each regimen, using the corresponding non-everolimus regimen as the reference. Associations were examined for the composite outcome of transplant rejection or death.</div></div><div><h3>Results</h3><div>The everolimus plus tacrolimus regimen showed lower reporting of the composite outcome compared with the tacrolimus regimen (ROR: 0.238 [95% confidence interval (CI): 0.073–0.782], <em>p</em> = 0.018; aROR: 0.258 [95% CI: 0.078–0.860], <em>p</em> = 0.027). For other regimens, including tacrolimus plus prednisone, cyclosporine, and cyclosporine plus prednisone plus mycophenolate mofetil, the addition of everolimus showed a consistent but non-significant trend toward lower reporting (all RORs &lt;1 and aRORs &lt;1).</div></div><div><h3>Conclusions</h3><div>Analysis of FAERS data identified a potential signal of lower reporting of transplant rejection or death associated with the addition of everolimus to certain immunosuppressive regimens in LTRs. These findings warrant cautious interpretation because of the inherent limitations of FAERS and require validation in prospective studies.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102345"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953296","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
Impact of induction agent selection on rejection, allograft function, and survival in kidney transplant recipients 诱导剂选择对肾移植受者排斥反应、同种异体移植功能和生存的影响。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-09 DOI: 10.1016/j.trim.2025.102341
Mohamad Saria Aldarwish , Wassim Toomah , Amro Idilbi , Roaa Ghanem , Mohamed Hussam Hallak , Alaa Alhalabi , Alia Alhassoun , Mohammad Mawaldi , Mohamad Amir Balloura , Emily C. Craver , Tambi Jarmi

Background

Kidney allograft rejection, driven by the recipient's immune response to non-self-HLA, remains a key barrier to kidney allograft survival. Induction therapy seeks to suppress early alloimmunity and reduce rejection. This study compares Basiliximab, Alemtuzumab, and Thymoglobulin in terms of acute rejection, kidney allograft function, and patients' survival.

Methods

A retrospective, single-center cohort study was conducted on 917 kidney transplant recipients between January 2019 and December 2023. Patients were stratified into Alemtuzumab (n = 337), Basiliximab (n = 300), and Thymoglobulin (n = 280) groups. The primary outcome was biopsy-proven acute rejection within the first 12 months post-transplant. Secondary outcomes included kidney allograft function. Kaplan-Meier survival analysis was performed to assess survival differences across groups.

Results

There was no statistically significant difference in acute rejection rates within the first 12 months among the three induction groups: Basiliximab (15 %), Thymoglobulin (14 %), and Alemtuzumab (9 %) (p = 0.16). Median creatinine clearance showed significant differences, with higher values in the Thymoglobulin (57.0 mL/min) and Alemtuzumab (56.0 mL/min) groups compared to the Basiliximab group (48.0 mL/min) (p = 0.003). Kaplan-Meier survival analysis demonstrated a statistically significant difference in patient survival over the 5-years follow-up period, with the highest survival observed in the Alemtuzumab group, followed by Thymoglobulin and then Basiliximab (p = 0.0067).

Conclusion

Basiliximab showed similar acute rejection rates to lymphocyte-depleting agents, suggesting it is not inferior in preventing early rejection when used for a selected group of patients. These findings support the need for further multi-center studies to better define optimal induction strategies and adapt therapy to individual patient profiles.
背景:由受体对非自身hla的免疫反应驱动的异体肾移植排斥反应仍然是异体肾移植存活的关键障碍。诱导疗法旨在抑制早期同种免疫,减少排斥反应。本研究比较了Basiliximab、Alemtuzumab和Thymoglobulin在急性排斥反应、同种异体肾移植功能和患者生存率方面的差异。方法:对2019年1月至2023年12月期间的917名肾移植受者进行回顾性、单中心队列研究。患者被分为阿仑单抗组(n = 337)、巴昔单抗组(n = 300)和胸腺球蛋白组(n = 280)。主要结果是移植后12个月内活检证实的急性排斥反应。次要结局包括肾移植功能。Kaplan-Meier生存分析评估各组间的生存差异。结果:Basiliximab(15%)、Thymoglobulin(14%)和Alemtuzumab(9%)三个诱导组在前12个月内的急性排斥率无统计学差异(p = 0.16)。中位肌酐清除率有显著差异,胸腺球蛋白组(57.0 mL/min)和阿仑单抗组(56.0 mL/min)高于巴昔昔单抗组(48.0 mL/min) (p = 0.003)。Kaplan-Meier生存分析显示,患者在5年随访期间的生存率有统计学意义,阿仑单抗组的生存率最高,其次是胸腺球蛋白,然后是巴昔昔单抗(p = 0.0067)。结论:Basiliximab显示出与淋巴细胞消耗药物相似的急性排斥率,表明它在预防早期排斥反应方面并不逊色,当用于选定的患者组时。这些发现支持了进一步多中心研究的需要,以更好地定义最佳诱导策略,并使治疗适应个体患者的情况。
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引用次数: 0
Smart transplant+: A HyCARE hybrid AI–cloud framework for intelligent donor–recipient matching, workflow automation, and post-transplant optimization 智能移植+:HyCARE混合人工智能云框架,用于智能供体-受体匹配、工作流程自动化和移植后优化。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-27 DOI: 10.1016/j.trim.2025.102332
Winner Pulakhandam , Archana Chaluvadi , Visrutatma Rao Vallu , R. Padmavathy
Organ transplantation is a life-saving medical intervention to reverse end-stage organ failure. Despite its life-saving potential, organ transplantation faces inefficiencies like organ shortages, long wait times, and rejection risks due to manual, clinically limited donor-recipient matching. The rapid growth of AI and cloud computing offers new opportunities to enhance organ transplantation. This study proposes Smart Transplant+, a HyCARE system enabling intelligent matching, decision-making, and process automation. The architecture leverages a huge Organ Transplant Dataset and the most advanced methods such as Feedforward Neural Networks and Genetic Algorithms to maximize donor-recipient matching. Gated Recurrent Units are utilized in pre-transplant risk prediction, and post-transplant care is augmented with real-time tracking by IoT-based wearable sensors. The system has been programmed using Python, along with software tools like TensorFlow for machine learning and AES encryption for secure data storage and transmission. The Smart Transplant+ system provides 95–98 % accuracy which is higher than existing methods in identifying suitable donors and recipients and the potential for successful transplantation, and greatly enhances organ transplant efficiency and success rate. This book illustrates the revolutionary potential of synergizing IoT, cloud technology, and AI to optimize transplant care and improve outcomes.
器官移植是一种挽救生命的医疗干预措施,以逆转终末期器官衰竭。尽管器官移植具有挽救生命的潜力,但由于人工、临床有限的供体-受体匹配,器官移植面临着器官短缺、等待时间长和排斥风险等低效率问题。人工智能和云计算的快速发展为加强器官移植提供了新的机遇。本研究提出了智能移植+,一个HyCARE系统,实现智能匹配,决策和过程自动化。该架构利用巨大的器官移植数据集和最先进的方法,如前馈神经网络和遗传算法,以最大限度地实现供体-受体匹配。门控复发单元用于移植前风险预测,移植后护理通过基于物联网的可穿戴传感器进行实时跟踪。该系统使用Python编程,以及用于机器学习的TensorFlow和用于安全数据存储和传输的AES加密等软件工具。智能移植+系统在识别合适的供体和受体以及移植成功的可能性方面提供95-98 %的准确率,大大提高了器官移植的效率和成功率。这本书说明了协同物联网、云技术和人工智能优化移植护理和改善结果的革命性潜力。
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引用次数: 0
Human leukocyte antigen-C*08 increases the risk of BK virus viremia in kidney transplant recipients 人白细胞抗原c *08增加肾移植受者发生BK病毒血症的风险
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.trim.2025.102340
Marie-Pier Thivierge, Stéphanie Béland, Olivier Désy, Sacha A. De Serres
BK virus (BKV) infection can cause graft loss in kidney transplant recipients. Several factors increase the risk of infection, including high level of immunosuppression, older age, and human leukocyte antigen (HLA) mismatch. The primary function of the major histocompatibility complex (HLA in human) is the presentation of peptides that originated from foreign or self-antigens to T cells to trigger an immune response, such as during infections. Identifying HLA genotypes that can influence the course of BKV infection could allow for stratifying patients according to their risk of developing the infection, thus personalizing the use of immunosuppressants. We conducted a retrospective study in a cohort of 1302 kidney transplant recipients, of whom 243 (19 %) developed BKV viremia. Clinical data and HLA genotype were evaluated for associations with BKV viremia. Among the 51 HLA genotypes analyzed, exploratory analysis revealed that patients expressing the HLA-C*08 genotype had a high risk of developing BKV viremia (p = 0.04). Using multivariate analyses adjusted for clinical variables that differed between patients with and without BK viremia (age and number of HLA-B mismatches), we confirmed that the HLA-C*08 genotype was associated with BK viremia. HLA-C*08, expressed by a sizeable proportion of the patients (82 individuals, or 6.3 % of the cohort), increased the risk of BKV viremia by 1.61 fold (p = 0.03). The HLA genotype may be useful in managing screening strategies for BKV in transplant recipients.
BK病毒(BKV)感染可导致肾移植受者移植物丢失。几个因素增加感染的风险,包括高水平的免疫抑制,年龄较大,和人类白细胞抗原(HLA)不匹配。主要组织相容性复合体(人类HLA)的主要功能是将源自外源或自身抗原的肽呈递到T细胞,以触发免疫反应,例如在感染期间。确定可以影响BKV感染过程的HLA基因型可以根据患者发生感染的风险对患者进行分层,从而使免疫抑制剂的使用个性化。我们对1302例肾移植受者进行了回顾性研究,其中243例(19% %)发生了BKV病毒血症。评估临床资料和HLA基因型与BKV病毒血症的关系。在分析的51个HLA基因型中,探索性分析发现表达HLA- c *08基因型的患者发生BKV病毒血症的风险较高(p = 0.04)。通过多变量分析调整了BK病毒血症患者和非BK病毒血症患者之间的临床变量差异(年龄和HLA-B错配次数),我们证实HLA-C*08基因型与BK病毒血症相关。相当大比例的患者(82例,占队列的6.3% %)表达HLA-C*08,使BKV病毒血症的风险增加了1.61倍(p = 0.03)。HLA基因型可能有助于移植受者BKV筛查策略的管理。
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引用次数: 0
Inhibition of USAG-1 improved delayed graft function in renal transplantation 抑制USAG-1可改善肾移植延迟移植功能。
IF 1.4 4区 医学 Q4 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.trim.2026.102348
Yongsheng Luo , Hongxuan Ma , Jiajia Sun, Xiaohu Li, Huimeng Wang, Minghui Qin, Hao Zhang, Haodong Bian, Jinfeng Li
Delayed graft function (DGF) is a critical complication following kidney transplantation. This study aimed to identify novel biomarkers and therapeutic targets for DGF. Transcriptomic data from the Gene Expression Omnibus (GEO) database were analyzed to screen for DGF-associated core genes. Serum levels of uterine sensitization-associated gene-1 (USAG-1) and kidney injury molecule-1 (KIM-1) were measured one day post-transplantation, and their predictive values for DGF were compared. Mouse models of DGF were established by inducing graded warm ischemia. USAG-1 was identified as a core gene significantly associated with DGF. Multivariate logistic regression identified USAG-1 as an independent risk factor for DGF (P < 0.05). Importantly, USAG-1 demonstrated superior diagnostic performance with an area under the curve (AUC) of 0.774 (95% CI: 0.660–0.895), which outperformed the traditional marker KIM-1 (AUC = 0.686; 95% CI: 0.559–0.831) (Pcomparison < 0.05). High USAG-1 expression was significantly correlated with prolonged recovery time (P < 0.05) and post-transplant dialysis duration (P < 0.05). In mouse models, USAG-1 knockout (KO) significantly increased survival (P < 0.05), improved renal pathology, and reduced the levels of injury markers (all P < 0.01), whereas exogenous USAG-1 supplementation reversed these effects (all P < 0.05). In conclusion, USAG-1 is a key regulator in DGF pathogenesis. Early postoperative serum USAG-1 levels can effectively predict DGF, and inhibition of USAG-1 expression may alleviate renal injury and promote functional recovery, offering potential diagnostic and therapeutic value in renal transplantation.
移植肾功能延迟(DGF)是肾移植术后的一个重要并发症。本研究旨在鉴定DGF的新生物标志物和治疗靶点。分析基因表达综合数据库(Gene Expression Omnibus, GEO)的转录组学数据,筛选dgf相关的核心基因。移植后1天测定子宫致敏相关基因1 (USAG-1)和肾损伤分子1 (KIM-1)的血清水平,并比较其对DGF的预测价值。采用诱导分级热缺血的方法建立小鼠DGF模型。USAG-1被鉴定为与DGF显著相关的核心基因。多因素logistic回归发现USAG-1是DGF的独立危险因素(P 比较)
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引用次数: 0
期刊
Transplant immunology
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