Pub Date : 2026-02-01Epub Date: 2026-01-09DOI: 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.
{"title":"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","authors":"Yeh-ching Linn, Kirubavathy Sundar Raj","doi":"10.1016/j.trim.2026.102344","DOIUrl":"10.1016/j.trim.2026.102344","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Method</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102344"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953262","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}
Pub Date : 2026-02-01Epub Date: 2026-01-09DOI: 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.
{"title":"TLR3 stimulation rejuvenates aged mesenchymal stem cells and restores immunosuppressive function in graft-versus-host disease","authors":"Linlin Jin , Ziqi Hu , Yuxin Huang , Haihui Xu , Nuo Li , Aoli Zhang , Yongjuan Duan , Peng Wu , Shuhai Lan , Jiarui Zheng , Tianyuan Hu , Yingchi Zhang","doi":"10.1016/j.trim.2026.102346","DOIUrl":"10.1016/j.trim.2026.102346","url":null,"abstract":"<div><div>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 (<em>p</em> < 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 (<em>p</em> < 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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102346"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953305","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}
Pub Date : 2026-02-01Epub Date: 2026-01-10DOI: 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.
{"title":"CD34+/CD3+ cells ratio in the peripheral blood stem cells product and graft-versus-host disease: Is there still room for improvement?","authors":"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","doi":"10.1016/j.trim.2026.102347","DOIUrl":"10.1016/j.trim.2026.102347","url":null,"abstract":"<div><div>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; <em>n</em> = 40), matched unrelated (group MUD; <em>n</em> = 28), mismatched unrelated (group MMUD; <em>n</em> = 6), and haploidentical (group haplo; <em>n</em> = 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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102347"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959912","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}
Pub Date : 2026-02-01Epub Date: 2025-11-29DOI: 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.
{"title":"Novel, short-course, low-dose total lymphoid irradiation (TLI) post heart transplant for recalcitrant rejection – A single centre experience","authors":"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","doi":"10.1016/j.trim.2025.102333","DOIUrl":"10.1016/j.trim.2025.102333","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods and results</h3><div>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 (<em>n</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102333"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655374","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}
Pub Date : 2026-02-01Epub Date: 2025-11-29DOI: 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.
{"title":"Conversion to belatacept-based immunosuppression as a calcineurin sparing regimen in lung transplant: A multi-institutional retrospective study","authors":"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","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}
Pub Date : 2026-02-01Epub Date: 2026-01-09DOI: 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 , Chihiro Shiraishi , 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 <1 and aRORs <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}
Pub Date : 2026-02-01Epub Date: 2025-12-09DOI: 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.
{"title":"Impact of induction agent selection on rejection, allograft function, and survival in kidney transplant recipients","authors":"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","doi":"10.1016/j.trim.2025.102341","DOIUrl":"10.1016/j.trim.2025.102341","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>A retrospective, single-center cohort study was conducted on 917 kidney transplant recipients between January 2019 and December 2023. Patients were stratified into Alemtuzumab (<em>n</em> = 337), Basiliximab (<em>n</em> = 300), and Thymoglobulin (<em>n</em> = 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.</div></div><div><h3>Results</h3><div>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 %) (<em>p</em> = 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) (<em>p</em> = 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 (<em>p</em> = 0.0067).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102341"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744824","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}
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.
{"title":"Smart transplant+: A HyCARE hybrid AI–cloud framework for intelligent donor–recipient matching, workflow automation, and post-transplant optimization","authors":"Winner Pulakhandam , Archana Chaluvadi , Visrutatma Rao Vallu , R. Padmavathy","doi":"10.1016/j.trim.2025.102332","DOIUrl":"10.1016/j.trim.2025.102332","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102332"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640344","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}
Pub Date : 2026-02-01Epub Date: 2025-12-04DOI: 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。
{"title":"Human leukocyte antigen-C*08 increases the risk of BK virus viremia in kidney transplant recipients","authors":"Marie-Pier Thivierge, Stéphanie Béland, Olivier Désy, Sacha A. De Serres","doi":"10.1016/j.trim.2025.102340","DOIUrl":"10.1016/j.trim.2025.102340","url":null,"abstract":"<div><div>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 (<em>p</em> = 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 (<em>p</em> = 0.03). The HLA genotype may be useful in managing screening strategies for BKV in transplant recipients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102340"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695893","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}
Pub Date : 2026-02-01Epub Date: 2026-01-09DOI: 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.
{"title":"Inhibition of USAG-1 improved delayed graft function in renal transplantation","authors":"Yongsheng Luo , Hongxuan Ma , Jiajia Sun, Xiaohu Li, Huimeng Wang, Minghui Qin, Hao Zhang, Haodong Bian, Jinfeng Li","doi":"10.1016/j.trim.2026.102348","DOIUrl":"10.1016/j.trim.2026.102348","url":null,"abstract":"<div><div>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. <em>USAG-1</em> was identified as a core gene significantly associated with DGF. Multivariate logistic regression identified USAG-1 as an independent risk factor for DGF (<em>P</em> < 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) (<em>P</em><sub><em>comparison</em></sub> < 0.05). High USAG-1 expression was significantly correlated with prolonged recovery time (<em>P</em> < 0.05) and post-transplant dialysis duration (<em>P</em> < 0.05). In mouse models, USAG-1 knockout (KO) significantly increased survival (<em>P</em> < 0.05), improved renal pathology, and reduced the levels of injury markers (all <em>P</em> < 0.01), whereas exogenous USAG-1 supplementation reversed these effects (all <em>P <</em> 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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102348"},"PeriodicalIF":1.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953254","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}