Pub 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":"2026-01-09","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 : 2026-01-09DOI: 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":"2026-01-09","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 : 2026-01-09DOI: 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":"2026-01-09","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 : 2026-01-09DOI: 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":"2026-01-09","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}
Pub Date : 2025-12-14DOI: 10.1016/j.trim.2025.102343
Szu-Tsen Yeh , Nicole A. Marshall , Brent P. Lehman , C. Dustin Rubinstein , Dhanansayan Shanmuganayagam , Jennifer J. Meudt , Robert R. Redfield III , Luis G. Hidalgo , Tanja Dominko , David D. Aufhauser
Background
Anti-pig antibodies, including those targeting porcine glycans and swine leukocyte antigens, present a significant challenge to pig-to-human xenotransplantation. Current strategies for managing these antibodies are limited. We examine the impact of standard antibody-mediated rejection (ABMR) therapy in human kidney transplant recipients on the levels of xenoreactive anti-pig antibodies.
Methods
We analyzed serum samples from 25 kidney transplant recipients with biopsy-proven ABMR treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. Anti-pig IgG and IgM titers were measured by flow cytometry. We assessed changes in anti-pig antibody mean fluorescence intensity (MFI) at baseline, 3, and 6 months post-treatment. We also correlated changes in anti-pig antibody levels with donor-specific anti-HLA antibodies (DSA).
Results
Rituximab-based ABMR therapy resulted in a modest reduction (∼21–29 % reduction) of anti-pig IgG levels at 3 months (p < 0.01) and at 6 months (p < 0.05). Anti-pig IgM levels demonstrated a similar but less consistent trend. Higher baseline DSA levels, particularly anti-HLA Class II, were associated with increased anti-pig IgG binding. However, the reductions in anti-pig antibodies did not correlate with changes in DSA levels post-treatment.
Conclusions
ABMR therapy that includes rituximab, IVIG, and corticosteroids leads to a modest decrease in anti-pig IgG levels, even when DSA levels are effectively neutralized. These findings highlight the limitations of current desensitization therapies and underscore the need for improved humoral-targeted therapies to support safe and durable clinical xenotransplantation.
{"title":"Rituximab-based antibody mediated rejection therapy modestly reduces Xenoreactive antibodies: Implications for pig-to-human xenotransplantation","authors":"Szu-Tsen Yeh , Nicole A. Marshall , Brent P. Lehman , C. Dustin Rubinstein , Dhanansayan Shanmuganayagam , Jennifer J. Meudt , Robert R. Redfield III , Luis G. Hidalgo , Tanja Dominko , David D. Aufhauser","doi":"10.1016/j.trim.2025.102343","DOIUrl":"10.1016/j.trim.2025.102343","url":null,"abstract":"<div><h3>Background</h3><div>Anti-pig antibodies, including those targeting porcine glycans and swine leukocyte antigens, present a significant challenge to pig-to-human xenotransplantation. Current strategies for managing these antibodies are limited. We examine the impact of standard antibody-mediated rejection (ABMR) therapy in human kidney transplant recipients on the levels of xenoreactive anti-pig antibodies.</div></div><div><h3>Methods</h3><div>We analyzed serum samples from 25 kidney transplant recipients with biopsy-proven ABMR treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. Anti-pig IgG and IgM titers were measured by flow cytometry. We assessed changes in anti-pig antibody mean fluorescence intensity (MFI) at baseline, 3, and 6 months post-treatment. We also correlated changes in anti-pig antibody levels with donor-specific anti-HLA antibodies (DSA).</div></div><div><h3>Results</h3><div>Rituximab-based ABMR therapy resulted in a modest reduction (∼21–29 % reduction) of anti-pig IgG levels at 3 months (<em>p</em> < 0.01) and at 6 months (<em>p</em> < 0.05). Anti-pig IgM levels demonstrated a similar but less consistent trend. Higher baseline DSA levels, particularly anti-HLA Class II, were associated with increased anti-pig IgG binding. However, the reductions in anti-pig antibodies did not correlate with changes in DSA levels post-treatment.</div></div><div><h3>Conclusions</h3><div>ABMR therapy that includes rituximab, IVIG, and corticosteroids leads to a modest decrease in anti-pig IgG levels, even when DSA levels are effectively neutralized. These findings highlight the limitations of current desensitization therapies and underscore the need for improved humoral-targeted therapies to support safe and durable clinical xenotransplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102343"},"PeriodicalIF":1.4,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769049","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 : 2025-12-10DOI: 10.1016/j.trim.2025.102342
Muhammad Zeeshan Ahmed , Sana Dilbar , Syeda Masooma Zahra Bukhari , Zareena Ali , Binyamin Wattoo , Sayra Tariq , Zeeshan Mutahir , Noreen Samad
Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals, including transplant recipients, neonates, and patients with immunosuppression. Despite extensive research, no effective vaccine exists—especially one leveraging mRNA technology. This study aimed to design a safe and immunogenic multi-epitope mRNA vaccine against HCMV using a comprehensive immunoinformatics approach. Glycoprotein B (gB), a highly conserved and immunodominant antigen, was selected as the vaccine target. B-cell, MHC-I, and MHC-II epitopes were predicted based on their antigenicity, immunogenicity, non-allergenicity, and non-toxicity. Of these, three B-cell binding epitopes, 3 MHC-II, and 4 MHC-I binding epitopes of T-cells, along with a toll-like receptor (TLR) agonist and an MHC I- targeting domain (MITD), were rationally assembled to design an mRNA vaccine construct (HCMVV). This construct was evaluated for physicochemical properties, population coverage, structural stability, interactions with innate receptors (TLR 2/4), and simulated immune responses. The vaccine showed high stability and favorable expression profiles, including ten conserved epitopes with broad MHC coverage, especially in South Asian populations. Docking studies indicated a stronger binding affinity for HCMVV–TLR 4 (− 19. 6 kcal/mol) compared to HCMVV–TLR 2 (− 14. 1 kcal/mol), characterized by high affinity and structural complementarity. Normal mode analysis confirmed complex stability, with average deformability per atom index for HCMVV, HCMVV–TLR 2, and HCMVV–TLR 4. Furthermore, molecular dynamics simulation (MDS) over 100 ns using GROMACS confirmed the stability of HCMVV–TLR2 and HCMVV–TLR4 complexes, with RMSD values below 2 Å (HCMVV–TLR4 more stable at <1.3 nm), low RMSF indicating rigidity (except specific flexible regions in TLR4), consistent hydrogen bonds (400–540), compact RoG (<2.7 nm for TLR4), stable SASA (370–430 nm2 with slight reduction in TLR4), and PCA revealing dominant conformational motions. Immune simulations predicted strong IgG and T-cell responses, as well as memory formation and efficient antigen clearance. This study introduces a promising mRNA vaccine candidate against HCMV with substantial immunogenic potential, especially for high-risk groups. However, experimental validation, including in vitro expression, in vivo immunogenicity, and protective efficacy studies, is essential to translate these computational findings into clinical applications.
{"title":"mRNA vaccine for human cytomegalovirus in immunocompromised hosts: An immunoinformatics approach","authors":"Muhammad Zeeshan Ahmed , Sana Dilbar , Syeda Masooma Zahra Bukhari , Zareena Ali , Binyamin Wattoo , Sayra Tariq , Zeeshan Mutahir , Noreen Samad","doi":"10.1016/j.trim.2025.102342","DOIUrl":"10.1016/j.trim.2025.102342","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals, including transplant recipients, neonates, and patients with immunosuppression. Despite extensive research, no effective vaccine exists—especially one leveraging mRNA technology. This study aimed to design a safe and immunogenic multi-epitope mRNA vaccine against HCMV using a comprehensive immunoinformatics approach. Glycoprotein B (gB), a highly conserved and immunodominant antigen, was selected as the vaccine target. B-cell, MHC-I, and MHC-II epitopes were predicted based on their antigenicity, immunogenicity, non-allergenicity, and non-toxicity. Of these, three B-cell binding epitopes, 3 MHC-II, and 4 MHC-I binding epitopes of T-cells, along with a toll-like receptor (TLR) agonist and an MHC I- targeting domain (MITD), were rationally assembled to design an mRNA vaccine construct (HCMVV). This construct was evaluated for physicochemical properties, population coverage, structural stability, interactions with innate receptors (TLR 2/4), and simulated immune responses. The vaccine showed high stability and favorable expression profiles, including ten conserved epitopes with broad MHC coverage, especially in South Asian populations. Docking studies indicated a stronger binding affinity for HCMVV–TLR 4 (− 19. 6 kcal/mol) compared to HCMVV–TLR 2 (− 14. 1 kcal/mol), characterized by high affinity and structural complementarity. Normal mode analysis confirmed complex stability, with average deformability per atom index for HCMVV, HCMVV–TLR 2, and HCMVV–TLR 4. Furthermore, molecular dynamics simulation (MDS) over 100 ns using GROMACS confirmed the stability of HCMVV–TLR2 and HCMVV–TLR4 complexes, with RMSD values below 2 Å (HCMVV–TLR4 more stable at <1.3 nm), low RMSF indicating rigidity (except specific flexible regions in TLR4), consistent hydrogen bonds (400–540), compact RoG (<2.7 nm for TLR4), stable SASA (370–430 nm<sup>2</sup> with slight reduction in TLR4), and PCA revealing dominant conformational motions. Immune simulations predicted strong IgG and T-cell responses, as well as memory formation and efficient antigen clearance. This study introduces a promising mRNA vaccine candidate against HCMV with substantial immunogenic potential, especially for high-risk groups. However, experimental validation, including in vitro expression, in vivo immunogenicity, and protective efficacy studies, is essential to translate these computational findings into clinical applications.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102342"},"PeriodicalIF":1.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744822","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 : 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":"2025-12-09","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}
Pub 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":"2025-12-04","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 : 2025-12-01DOI: 10.1016/j.trim.2025.102331
Serafettin Okutan , Hasan Saritas , Serdar Saritas , Semra Bulbuloglu , Hüseyin Guneş
Background
The end-stage liver diseases require liver transplantation as the life-saving solution. It is known that monocytes/macrophages and high-density lipoprotein cholesterol (HDLC) have important contributions to the development of hepatic inflammation and oxidative stress before liver transplantation. However, the effect of monocyte/HDL-C ratio (MHR) on clinical progression and outcome in the post-transplant period are not fully understood. Our hypothesis is that the MHR value may be associated with poor vs. good outcomes after liver transplantation.
Methods
In our retrospective study, we included 464 liver transplant recipients. Patients' data were extracted from electronic and other paper records in our teaching/research hospital. The MHR values and other blood parameters (creatinine, total protein, albumin, etc.) were expressed as a mean and standard deviation, which were analyzed by the Pearson correlation test. The relationship between graft dysfunction and MHR was determined by ROC curve analysis.
Results
The mean age of liver transplant recipients was 45.8 ± 13.7 years. Nineteen percent of patients had liver failure due to Alcoholic Fatty Liver Disease (AFLD) and 34.5 % had liver failure due to hepatitis B virus. At the end of 3 months after liver transplantation, 84.5 % of liver transplant recipients were alive, 5.8 % experienced graft rejection and 5.17 % had an infection. There was a statistically significant improvement in total protein, albumin, liver function tests, and serum creatinine values of the survivors (all p < 0.05). The MHR levels were significantly higher in patients who died after transplantation in comparison to those who survived before and after liver transplantation and these differences were statistically significant (p < 0.01).
Conclusion
The increased MHR values of recipients after liver transplantation correlated with their risk of survival. Furthermore, the MHR value increased with increased MELD score and the number of days of hospitalization and was not affected by gender and age. MHR was higher in patients with chronic diseases. Patients with high MHR before and after transplantation should be monitored more closely in the perioperative period.
{"title":"Relation between monocyte to high-density lipoprotein cholesterol ratio and prognosis in recipients after liver transplantation","authors":"Serafettin Okutan , Hasan Saritas , Serdar Saritas , Semra Bulbuloglu , Hüseyin Guneş","doi":"10.1016/j.trim.2025.102331","DOIUrl":"10.1016/j.trim.2025.102331","url":null,"abstract":"<div><h3>Background</h3><div>The end-stage liver diseases require liver transplantation as the life-saving solution. It is known that monocytes/macrophages and high-density lipoprotein cholesterol (HDL<img>C) have important contributions to the development of hepatic inflammation and oxidative stress before liver transplantation. However, the effect of monocyte/HDL-C ratio (MHR) on clinical progression and outcome in the post-transplant period are not fully understood. Our hypothesis is that the MHR value may be associated with poor vs. good outcomes after liver transplantation.</div></div><div><h3>Methods</h3><div>In our retrospective study, we included 464 liver transplant recipients. Patients' data were extracted from electronic and other paper records in our teaching/research hospital. The MHR values and other blood parameters (creatinine, total protein, albumin, etc.) were expressed as a mean and standard deviation, which were analyzed by the Pearson correlation test. The relationship between graft dysfunction and MHR was determined by ROC curve analysis.</div></div><div><h3>Results</h3><div>The mean age of liver transplant recipients was 45.8 ± 13.7 years. Nineteen percent of patients had liver failure due to Alcoholic Fatty Liver Disease (AFLD) and 34.5 % had liver failure due to hepatitis B virus. At the end of 3 months after liver transplantation, 84.5 % of liver transplant recipients were alive, 5.8 % experienced graft rejection and 5.17 % had an infection. There was a statistically significant improvement in total protein, albumin, liver function tests, and serum creatinine values of the survivors (all <em>p</em> < 0.05). The MHR levels were significantly higher in patients who died after transplantation in comparison to those who survived before and after liver transplantation and these differences were statistically significant (<em>p</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>The increased MHR values of recipients after liver transplantation correlated with their risk of survival. Furthermore, the MHR value increased with increased MELD score and the number of days of hospitalization and was not affected by gender and age. MHR was higher in patients with chronic diseases. Patients with high MHR before and after transplantation should be monitored more closely in the perioperative period.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102331"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614841","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 : 2025-11-29DOI: 10.1016/j.trim.2025.102329
David Garrido , Verónica Jeréz , Jorge Huertas
Background: Chronic kidney disease is a major public health concern for which kidney transplantation offers the best survival benefit. Patients with high calculated panel-reactive antibody (cPRA) levels often face extended waiting times owing to donor compatibility challenges.
Methods: We conducted a descriptive, cross-sectional analysis of all 724 kidney transplant candidates on Ecuador's national waiting list between 2011 and 2022, using anonymized INDOT data. cPRA values were obtained with solid-phase, bead-based luminometric assays. We applied descriptive statistics, Joinpoint regression to assess temporal trends, Spearman correlation for cPRA versus waiting time, chi-square tests for categorical comparisons, and logistic regression to estimate odds ratios (ORs) for prolonged waiting time (>5 years).
Results: Overall, 166 candidates (22.9 %) had cPRA ≥20 %. Of these, 86 (51.8 %) exhibited cPRA ≥75 %. The number of sensitized patients with cPRA ≥75 % rose from one in 2011 to nineteen in 2022 (annual percent change 10.4 %). Median waiting time was 54.5 months for candidates with cPRA ≥75 % versus 51.5 months for those with cPRA 20–74 %; there was no linear correlation between cPRA and waiting time (ρ = 0.11, p = 0.18). However, candidates with cPRA ≥75 % were more likely to wait >5 years than those below this threshold (44.2 % vs. 25.0 %; OR 2.38; p = 0.01), and a similar pattern was observed for candidates with cPRA ≥70 % (OR 2.98; p = 0.003).
Conclusion: The proportion of highly sensitized candidates has increased substantially between 2011 and 2022. Patients with cPRA levels ≥75 % were associated with prolonged waitlist time to obtain a kidney transplant. Prospective studies are warranted to explore underlying mechanisms and inform allocation strategies.
背景：慢性肾脏疾病是一个主要的公共卫生问题，肾移植提供了最佳的生存效益。由于供体相容性的挑战，计算出的高反应性抗体（cPRA）水平的患者往往面临延长的等待时间。方法：我们使用匿名INDOT数据，对2011年至2022年厄瓜多尔全国等待名单上的所有724名肾移植候选人进行了描述性横断面分析。cPRA值采用固相、珠状荧光法测定。我们应用描述性统计、连接点回归来评估时间趋势、cPRA与等待时间的Spearman相关性、卡方检验来进行分类比较、逻辑回归来估计等待时间延长（>；5年）的优势比（ORs）。结果：总体而言，166名候选人（22.9%）的cPRA≥20%。其中，86例（51.8%）cPRA≥75%。cPRA≥75%致敏患者的数量从2011年的1例增加到2022年的19例（年变化10.4%）。cPRA≥75%的候选者中位等待时间为54.5个月，而cPRA 20 - 74%的候选者中位等待时间为51.5个月；cPRA与等待时间无线性相关（ρ = 0.11, p = 0.18）。然而，cPRA≥75%的患者比低于该阈值的患者更有可能等待5年（44.2% vs. 25.0%; OR 2.38; p = 0.01）， cPRA≥70%的患者也有类似的情况（OR 2.98; p = 0.003）。结论：2011年至2022年间，高敏感候选人比例大幅增加。cPRA水平≥75%的患者与获得肾移植的等待时间延长相关。有必要进行前瞻性研究，以探索潜在的机制并为分配策略提供信息。
{"title":"Temporal dynamics of cPRA levels and their categorical impact on waitlist longevity in Ecuadorian kidney transplant candidates: A 2011–2022 Nationwide cohort analysis","authors":"David Garrido , Verónica Jeréz , Jorge Huertas","doi":"10.1016/j.trim.2025.102329","DOIUrl":"10.1016/j.trim.2025.102329","url":null,"abstract":"<div><div>Background: Chronic kidney disease is a major public health concern for which kidney transplantation offers the best survival benefit. Patients with high calculated panel-reactive antibody (cPRA) levels often face extended waiting times owing to donor compatibility challenges.</div><div>Methods: We conducted a descriptive, cross-sectional analysis of all 724 kidney transplant candidates on Ecuador's national waiting list between 2011 and 2022, using anonymized INDOT data. cPRA values were obtained with solid-phase, bead-based luminometric assays. We applied descriptive statistics, Joinpoint regression to assess temporal trends, Spearman correlation for cPRA versus waiting time, chi-square tests for categorical comparisons, and logistic regression to estimate odds ratios (ORs) for prolonged waiting time (>5 years).</div><div>Results: Overall, 166 candidates (22.9 %) had cPRA ≥20 %. Of these, 86 (51.8 %) exhibited cPRA ≥75 %. The number of sensitized patients with cPRA ≥75 % rose from one in 2011 to nineteen in 2022 (annual percent change 10.4 %). Median waiting time was 54.5 months for candidates with cPRA ≥75 % versus 51.5 months for those with cPRA 20–74 %; there was no linear correlation between cPRA and waiting time (ρ = 0.11, <em>p</em> = 0.18). However, candidates with cPRA ≥75 % were more likely to wait >5 years than those below this threshold (44.2 % vs. 25.0 %; OR 2.38; <em>p</em> = 0.01), and a similar pattern was observed for candidates with cPRA ≥70 % (OR 2.98; <em>p</em> = 0.003).</div><div>Conclusion: The proportion of highly sensitized candidates has increased substantially between 2011 and 2022. Patients with cPRA levels ≥75 % were associated with prolonged waitlist time to obtain a kidney transplant. Prospective studies are warranted to explore underlying mechanisms and inform allocation strategies.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102329"},"PeriodicalIF":1.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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