Pub Date : 2025-09-02DOI: 10.1016/j.trim.2025.102285
Qixuan Li , Zhaoying Pang , Meng Yang , Lunli Xiang , Xulian Hu , Qin Yang , Hongwen Zhao , Jie Li , Xiaosong Xu
Background
Kidney transplantation (KT) stands as a highly effective, life-saving intervention for patients with end-stage renal disease, offering substantial improvements in both quality of life and long-term survival. However, one of the most critical challenges that can arise in this procedure is hyperacute rejection (HR). This severe immune response occurs almost immediately after transplantation and can place the patient at a heightened risk of serious complications and even drastically jeopardizes the survival of the transplanted kidney. This study reports a case of HR mediated by colony-stimulating factor 2 (CSF2) antibodies following living-related KT, elaborates on its clinical features, diagnostic workflow, and therapeutic management, and analyzes the role of CSF2 antibodies in KT-related immunity. The findings aim to provide clinical reference for optimizing HR prevention and management in KT practice.
{"title":"Case report: Hyperacute rejection of living relative kidney transplantation caused by colony-stimulating factor 2 antibodies","authors":"Qixuan Li , Zhaoying Pang , Meng Yang , Lunli Xiang , Xulian Hu , Qin Yang , Hongwen Zhao , Jie Li , Xiaosong Xu","doi":"10.1016/j.trim.2025.102285","DOIUrl":"10.1016/j.trim.2025.102285","url":null,"abstract":"<div><h3>Background</h3><div>Kidney transplantation (KT) stands as a highly effective, life-saving intervention for patients with end-stage renal disease, offering substantial improvements in both quality of life and long-term survival. However, one of the most critical challenges that can arise in this procedure is hyperacute rejection (HR). This severe immune response occurs almost immediately after transplantation and can place the patient at a heightened risk of serious complications and even drastically jeopardizes the survival of the transplanted kidney. This study reports a case of HR mediated by colony-stimulating factor 2 (CSF2) antibodies following living-related KT, elaborates on its clinical features, diagnostic workflow, and therapeutic management, and analyzes the role of CSF2 antibodies in KT-related immunity. The findings aim to provide clinical reference for optimizing HR prevention and management in KT practice.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102285"},"PeriodicalIF":1.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001128","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}
Lung transplantation (LTx) is increasingly performed worldwide, yet post-transplant survival remains lower than for other solid organs. Diabetes mellitus (DM) is common among LTx recipients and impacts outcomes. This systematic review evaluates the effects of DM on LTx outcomes and the influence of diabetes onset timing on survival.
Methods
A systematic search was conducted in December 2024 across PubMed, Scopus, and Web of Science to identify original studies or case series involving patients with pre-transplant DM undergoing or waitlisted for LTx. The quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS).
Results
Eighty-four studies published between 1992 and 2024 were included, with sample sizes ranging from 10 to over 4 million patients and follow-up from 1 to 25 years. Diabetes was present in 8–56 % of lung transplant recipients. Patients with diabetes, including pre-existing diabetes, cystic fibrosis-related diabetes (CFRD), and new-onset diabetes after transplantation (NODAT), showed higher risks of infections, acute kidney injury, thromboembolic events, chronic lung allograft dysfunction, and cardiovascular complications. Diabetes was consistently associated with increased short- and long-term mortality, prolonged mechanical ventilation, and greater hospitalization rates.
Conclusion
Diabetes—whether present before or developing after lung transplantation—is a significant predictor of adverse clinical outcomes and mortality. These findings underscore the need for careful perioperative glycemic management, tailored immunosuppression, and vigilant monitoring to reduce complications. Further standardized, prospective research is essential to guide optimal diabetes management and improve survival in lung transplant recipients.
背景和目的：肺移植（LTx）越来越多地在世界范围内进行，但移植后生存率仍然低于其他实体器官。糖尿病（DM）在LTx接受者中很常见，并影响预后。本系统综述评估了糖尿病对LTx结局的影响以及糖尿病发病时间对生存的影响。方法：于2024年12月对PubMed、Scopus和Web of Science进行系统检索，以确定涉及移植前糖尿病患者接受或等待LTx的原始研究或病例系列。纳入研究的质量采用非随机研究方法学指数（Methodological Index for non - random studies，未成年人）进行评估。结果：纳入了1992年至2024年间发表的84项研究，样本量从10万到400多万患者不等，随访时间为1至25 年。8- 56%的肺移植受者存在糖尿病 %。糖尿病患者，包括既往糖尿病、囊性纤维化相关糖尿病（CFRD）和移植后新发糖尿病（NODAT），感染、急性肾损伤、血栓栓塞事件、慢性同种异体肺功能障碍和心血管并发症的风险更高。糖尿病始终与增加的短期和长期死亡率、延长的机械通气时间和更高的住院率相关。结论：糖尿病——无论是在肺移植前出现还是在肺移植后发生——是不良临床结果和死亡率的重要预测因子。这些发现强调了围手术期谨慎的血糖管理、量身定制的免疫抑制和警惕监测以减少并发症的必要性。进一步标准化的前瞻性研究对于指导最佳糖尿病管理和提高肺移植受者的生存率至关重要。
{"title":"Lung transplantation in patients with diabetes: A systematic review","authors":"Fatemeh Moosaie , Shiva Abedinzadeh , Sepide Javankiani , Fatemeh Asli , Prajjwol Luitel , Seyede Marzie Fatemi Abhari","doi":"10.1016/j.trim.2025.102279","DOIUrl":"10.1016/j.trim.2025.102279","url":null,"abstract":"<div><h3>Background and aim</h3><div>Lung transplantation (LTx) is increasingly performed worldwide, yet post-transplant survival remains lower than for other solid organs. Diabetes mellitus (DM) is common among LTx recipients and impacts outcomes. This systematic review evaluates the effects of DM on LTx outcomes and the influence of diabetes onset timing on survival.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in December 2024 across PubMed, Scopus, and Web of Science to identify original studies or case series involving patients with pre-transplant DM undergoing or waitlisted for LTx. The quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS).</div></div><div><h3>Results</h3><div>Eighty-four studies published between 1992 and 2024 were included, with sample sizes ranging from 10 to over 4 million patients and follow-up from 1 to 25 years. Diabetes was present in 8–56 % of lung transplant recipients. Patients with diabetes, including pre-existing diabetes, cystic fibrosis-related diabetes (CFRD), and new-onset diabetes after transplantation (NODAT), showed higher risks of infections, acute kidney injury, thromboembolic events, chronic lung allograft dysfunction, and cardiovascular complications. Diabetes was consistently associated with increased short- and long-term mortality, prolonged mechanical ventilation, and greater hospitalization rates.</div></div><div><h3>Conclusion</h3><div>Diabetes—whether present before or developing after lung transplantation—is a significant predictor of adverse clinical outcomes and mortality. These findings underscore the need for careful perioperative glycemic management, tailored immunosuppression, and vigilant monitoring to reduce complications. Further standardized, prospective research is essential to guide optimal diabetes management and improve survival in lung transplant recipients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102279"},"PeriodicalIF":1.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001147","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 : 2025-08-24DOI: 10.1016/j.trim.2025.102278
Fei Xue , Xuanpeng Wu , Ming Ni , Tao Jiang , Hao Wang , Yunfeng Ma , Qifei Wu
Post-transplant rejection is a serious problem for patients undergoing organ transplantation. It is currently believed that immune-related factors are the main causes of transplant rejection, but the roles of many immune cell phenotypes are still unclear.
We utilized Mendelian randomization analysis to explore the association between 731 immune cell and the risk of transplant rejection.
We systematically analyzed 731 immune cell phenotypes (including absolute counts, surface markers, and functional states) from peripheral blood of 3657 European individuals. Genetic instruments were selected at a genome-wide significance threshold (p < 1 × 10−5) to assess bidirectional causal relationships with transplant rejection events from FinnGen biobank (n = 16,380,395 SNPs). Forward MR analysis identified 33 immune phenotypes significantly associated with rejection risk: 19 protective (odds ratio [OR] < 1, p < 0.05) predominantly in B cell subsets, and 14 risk-enhancing phenotypes (OR > 1). Reverse MR revealed that rejection events causally altered 34 immune phenotypes, upregulated 18 effector phenotypes and downregulated 16 regulatory phenotypes. Sensitivity analyses confirmed robustness against pleiotropy (MR-Egger intercept p > 0.05, MR-PRESSO global test p > 0.01 and heterogeneity test p > 0.05). These findings highlight the dynamic interplay between B cell plasticity and Treg depletion in transplant outcomes, suggesting novel therapeutic targets for rejection prevention.
Our research confirms the close relationship between transplant rejection and immune cells, especially that certain B cell subsets are causally linked to a lower risk of transplant rejection, providing new targets and insights for future clinical treatments.
{"title":"Exploration of causal relationship between transplant rejection and immune cells: A two-sample Mendelian randomization study","authors":"Fei Xue , Xuanpeng Wu , Ming Ni , Tao Jiang , Hao Wang , Yunfeng Ma , Qifei Wu","doi":"10.1016/j.trim.2025.102278","DOIUrl":"10.1016/j.trim.2025.102278","url":null,"abstract":"<div><div>Post-transplant rejection is a serious problem for patients undergoing organ transplantation. It is currently believed that immune-related factors are the main causes of transplant rejection, but the roles of many immune cell phenotypes are still unclear.</div><div>We utilized Mendelian randomization analysis to explore the association between 731 immune cell and the risk of transplant rejection.</div><div>We systematically analyzed 731 immune cell phenotypes (including absolute counts, surface markers, and functional states) from peripheral blood of 3657 European individuals. Genetic instruments were selected at a genome-wide significance threshold (<em>p</em> < 1 × 10<sup>−5</sup>) to assess bidirectional causal relationships with transplant rejection events from FinnGen biobank (<em>n</em> = 16,380,395 SNPs). Forward MR analysis identified 33 immune phenotypes significantly associated with rejection risk: 19 protective (odds ratio [OR] < 1, <em>p</em> < 0.05) predominantly in B cell subsets, and 14 risk-enhancing phenotypes (OR > 1). Reverse MR revealed that rejection events causally altered 34 immune phenotypes, upregulated 18 effector phenotypes and downregulated 16 regulatory phenotypes. Sensitivity analyses confirmed robustness against pleiotropy (MR-Egger intercept <em>p</em> > 0.05, MR-PRESSO global test <em>p</em> > 0.01 and heterogeneity test p > 0.05). These findings highlight the dynamic interplay between B cell plasticity and Treg depletion in transplant outcomes, suggesting novel therapeutic targets for rejection prevention.</div><div>Our research confirms the close relationship between transplant rejection and immune cells, especially that certain B cell subsets are causally linked to a lower risk of transplant rejection, providing new targets and insights for future clinical treatments.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102278"},"PeriodicalIF":1.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904580","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 : 2025-08-07DOI: 10.1016/j.trim.2025.102275
Muchen Liu , Zhongyu Kang , Huan Zhang
Background
Donor-specific antibodies (DSAs) are a major risk factor for adverse clinical outcomes in hematopoietic stem cell transplantation (HSCT). However, their clinical relevance remains controversial and unclear. This meta-analysis evaluated the impact of DSAs in HSCT.
Methods
This systematic review and meta-analysis compared outcomes between patients positive and negative for DSAs. Databases including PubMed, Embase, and Cochrane Library were searched for English-language studies published up to January 2025. Studies assessing DSAs and outcomes, including overall survival (OS), graft failure, poor graft function (PGF), poor engraftment rates, and graft-versus-host disease (GVHD). Pooled odds ratios and confidence intervals were calculated using fixed- or random-effects models.
Results
Thirty-two studies with 5555 patients with HSCT (557 DSA-positive, 4998 DSA-negative) were included. DSA positivity was considerably associated with increased risk of PGF, graft failure, and overall mortality. Additionally, patients with DSA-positive had lower OS. However, no notable associations were found with GVHD, neutrophil or platelet engraftment, relapse, or infections such as cytomegalovirus or Epstein-Barr virus. Study heterogeneity was moderate to high for several outcomes, necessitating the use of random-effects models.
Conclusion
DSAs are linked to poorer HSCT outcomes, particularly graft failure and reduced overall survival. Routine DSA screening and targeted interventions may improve outcomes.
{"title":"Impacts of donor-specific anti-HLA antibodies on post-transplant clinical outcomes in hematopoietic stem cell transplantation: A systematic review and meta-analysis","authors":"Muchen Liu , Zhongyu Kang , Huan Zhang","doi":"10.1016/j.trim.2025.102275","DOIUrl":"10.1016/j.trim.2025.102275","url":null,"abstract":"<div><h3>Background</h3><div>Donor-specific antibodies (DSAs) are a major risk factor for adverse clinical outcomes in hematopoietic stem cell transplantation (HSCT). However, their clinical relevance remains controversial and unclear. This meta-analysis evaluated the impact of DSAs in HSCT.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis compared outcomes between patients positive and negative for DSAs. Databases including PubMed, Embase, and Cochrane Library were searched for English-language studies published up to January 2025. Studies assessing DSAs and outcomes, including overall survival (OS), graft failure, poor graft function (PGF), poor engraftment rates, and graft-versus-host disease (GVHD). Pooled odds ratios and confidence intervals were calculated using fixed- or random-effects models.</div></div><div><h3>Results</h3><div>Thirty-two studies with 5555 patients with HSCT (557 DSA-positive, 4998 DSA-negative) were included. DSA positivity was considerably associated with increased risk of PGF, graft failure, and overall mortality. Additionally, patients with DSA-positive had lower OS. However, no notable associations were found with GVHD, neutrophil or platelet engraftment, relapse, or infections such as cytomegalovirus or Epstein-Barr virus. Study heterogeneity was moderate to high for several outcomes, necessitating the use of random-effects models.</div></div><div><h3>Conclusion</h3><div>DSAs are linked to poorer HSCT outcomes, particularly graft failure and reduced overall survival. Routine DSA screening and targeted interventions may improve outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102275"},"PeriodicalIF":1.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812453","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 : 2025-08-07DOI: 10.1016/j.trim.2025.102276
Shujun Yang , Hao Wei , Haihong Yang , Xilong Lin , Panfeng Shang , Shengkun Sun
Kidney transplantation is the only effective treatment for patients with end-stage renal disease (ESRD). With the application of gene-editing technology and modern immunosuppressants, kidney transplants from pigs with up to 12 edited genes have shown significant survival in non-human primates (NHP) and have been transplanted in handful of patients. Our review describes the most current progress in gene-edited pigs used for kidney xenotransplantation (KXTx) to NHP. Furthermore, this review reports about drug treatment options such as immune induction, immune maintenance, anti-inflammatory therapy, and anticoagulant therapy aiming to provide in prospects of KXTx. We stress the following highlights: 1) The application of induction and maintenance therapies with gene edited pigs for NHP KXTx; 2) The application of CD40-CD154 co-stimulatory pathway blockers as essential in immune maintenance medication; 3) The role of cytokines in monitoring of anti-inflammatory treatment’ and 4) The salvage administration measures during suspected rejection reactions can to some extent prolong the functional survival of the recipient kidney.
{"title":"Research progress and current status of gene-edited-pig to non-human primate kidney xenotransplantation drug application","authors":"Shujun Yang , Hao Wei , Haihong Yang , Xilong Lin , Panfeng Shang , Shengkun Sun","doi":"10.1016/j.trim.2025.102276","DOIUrl":"10.1016/j.trim.2025.102276","url":null,"abstract":"<div><div>Kidney transplantation is the only effective treatment for patients with end-stage renal disease (ESRD). With the application of gene-editing technology and modern immunosuppressants, kidney transplants from pigs with up to 12 edited genes have shown significant survival in non-human primates (NHP) and have been transplanted in handful of patients. Our review describes the most current progress in gene-edited pigs used for kidney xenotransplantation (KXTx) to NHP. Furthermore, this review reports about drug treatment options such as immune induction, immune maintenance, anti-inflammatory therapy, and anticoagulant therapy aiming to provide in prospects of KXTx. We stress the following highlights: 1) The application of induction and maintenance therapies with gene edited pigs for NHP KXTx; 2) The application of CD40-CD154 co-stimulatory pathway blockers as essential in immune maintenance medication; 3) The role of cytokines in monitoring of anti-inflammatory treatment’ and 4) The salvage administration measures during suspected rejection reactions can to some extent prolong the functional survival of the recipient kidney.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102276"},"PeriodicalIF":1.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812454","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 : 2025-08-06DOI: 10.1016/j.trim.2025.102269
George E. Nita , Alex Rothwell , Matthew Howse , Dan Ridgway , Abdul Hammad , Sanjay Mehra , Andrew R. Jones , Petra Goldsmith
Introduction
The development of de novo donor-specific antibodies (DSAs) against HLA is associated with premature graft failure in kidney transplantation. However, reported rates and contributing factors vary widely. We aimed to identify pre-transplant factors influencing de novo HLA-specific antibody development using machine learning (ML).
Methods
Data from 460 kidney transplant recipients at a single centre (2009–2014) was analysed. Pre-transplant clinical and immunological variables were collected, and post-transplant sera were screened for HLA antibodies. Positive samples underwent Single Antigen Bead (SAB) testing. ML models (CART, RF, XGBoost, CatBoost) were trained on a set of pre-transplant data to predict dnDSA formation, with and without SMOTE oversampling. Model performance was evaluated using F1 scores, and feature importance was assessed using SHAP.
Results
In the full cohort, 115 patients (25 %) developed dnHLA-specific antibodies, including 36 (31 %) with dnDSAs. XGBoost achieved the best performance (F1 0.54–0.59 without SMOTE; 0.72–0.79 with SMOTE). Univariate analysis identified significant predictors: pre-transplant HLA-specific antibodies (p < 0.001), prior transplantation (p < 0.001), cold ischaemia time (CIT) (p = 0.02), female gender (p = 0.01), younger age (p = 0.03), HLA mismatch (p = 0.01), aminoacid mismatch (p = 0.01), and depleting induction (p = 0.01). SHAP plots confirmed the importance of pre-existing antibodies and re-transplantation. Extremes of CIT and age ≥ 65 was associated were associated with reduced predicted risk. Model performance in the unsensitised subgroup was limited (F1 < 0.2).
Conclusion
ML models can be used to identify pre-transplant risk factors for de novo HLA-specific antibody development. Monitoring and risk-stratification based on these factors may inform immunological strategies and recipient selection to improve long-term allograft outcomes.
Translational statement
This study identified pre-transplant risk factors for the development of de novo DSA in kidney transplantation. Monitoring and risk-stratifying patients based on these factors may help guide preventive immunological strategies and recipient selection to improve long-term allograft outcomes.
{"title":"Using machine learning to examine pre-transplant factors influencing De novo HLA-specific antibody development post-kidney transplant","authors":"George E. Nita , Alex Rothwell , Matthew Howse , Dan Ridgway , Abdul Hammad , Sanjay Mehra , Andrew R. Jones , Petra Goldsmith","doi":"10.1016/j.trim.2025.102269","DOIUrl":"10.1016/j.trim.2025.102269","url":null,"abstract":"<div><h3>Introduction</h3><div>The development of <em>de novo</em> donor-specific antibodies (DSAs) against HLA is associated with premature graft failure in kidney transplantation. However, reported rates and contributing factors vary widely. We aimed to identify pre-transplant factors influencing <em>de novo</em> HLA-specific antibody development using machine learning (ML).</div></div><div><h3>Methods</h3><div>Data from 460 kidney transplant recipients at a single centre (2009–2014) was analysed. Pre-transplant clinical and immunological variables were collected, and post-transplant sera were screened for HLA antibodies. Positive samples underwent Single Antigen Bead (SAB) testing. ML models (CART, RF, XGBoost, CatBoost) were trained on a set of pre-transplant data to predict <em>dn</em>DSA formation, with and without SMOTE oversampling. Model performance was evaluated using F1 scores, and feature importance was assessed using SHAP.</div></div><div><h3>Results</h3><div>In the full cohort, 115 patients (25 %) developed <em>dn</em>HLA-specific antibodies, including 36 (31 %) with <em>dn</em>DSAs. XGBoost achieved the best performance (F1 0.54–0.59 without SMOTE; 0.72–0.79 with SMOTE). Univariate analysis identified significant predictors: pre-transplant HLA-specific antibodies (<em>p</em> < 0.001), prior transplantation (p < 0.001), cold ischaemia time (CIT) (<em>p</em> = 0.02), female gender (<em>p</em> = 0.01), younger age (<em>p</em> = 0.03), HLA mismatch (p = 0.01), aminoacid mismatch (p = 0.01), and depleting induction (p = 0.01). SHAP plots confirmed the importance of pre-existing antibodies and re-transplantation. Extremes of CIT and age ≥ 65 was associated were associated with reduced predicted risk. Model performance in the unsensitised subgroup was limited (F1 < 0.2).</div></div><div><h3>Conclusion</h3><div>ML models can be used to identify pre-transplant risk factors for <em>de novo</em> HLA-specific antibody development. Monitoring and risk-stratification based on these factors may inform immunological strategies and recipient selection to improve long-term allograft outcomes.</div></div><div><h3>Translational statement</h3><div>This study identified pre-transplant risk factors for the development of <em>de novo</em> DSA in kidney transplantation. Monitoring and risk-stratifying patients based on these factors may help guide preventive immunological strategies and recipient selection to improve long-term allograft outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102269"},"PeriodicalIF":1.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804933","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 : 2025-08-05DOI: 10.1016/j.trim.2025.102274
Joanna Dębska-Zielkowska , Bartosz Słomiński , Hanna Zielińska , Anna Dukat-Mazurek , Grażyna Moszkowska , Maria Bieniaszewska , Jan Maciej Zaucha , Piotr Trzonkowski , Maciej Zieliński
Background
Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient.
Methods
We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [n = 24 with acute myeloid leukemia (AML), n = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and n = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors.
Results
Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD (p = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 × 109 cells/L) under 28 days (p = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients (r = 0.9932).
Conclusion
Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.
背景：自然杀伤细胞（NK）表达杀伤免疫球蛋白样受体（KIRs），该受体调节NK细胞的功能。自体人白细胞抗原（HLA） I类分子作为kir的抑制分子，阻断NK细胞的杀伤活性。由于正常NK活性可能会影响来自HLA匹配的同胞供体的造血干细胞移植（HSCT）或骨髓移植（BMT）的结果，我们研究了NK细胞上呈现的kir和I类HLA之间的相互作用。移植受体体内I类HLA配体抑制剂表达不足可能导致移植物抗宿主病（GvHD）或移植排斥等并发症。方法：我们研究了缺失KIR配体（MSL）和KIR单倍型对HSCT患者GvHD发展、复发、死亡、感染和细胞恢复的影响。本组纳入59例患者[n = 24例急性髓性白血病（AML）， n = 12例慢性髓性白血病（CML）， n = 12例骨髓增生异常综合征（MDS）， n = 11例急性淋巴细胞白血病（ALL）]，他们接受了来自兄弟姐妹供体的HSCT/BMT。结果：我们的研究结果显示，单倍型AA在MDS患者的供体中比Bx更常见，并且与慢性(c) GvHD的发生率较高相关（p = 0.003）。在该组中，我们还观察到AA供体单倍型与28 天内0.5 G/l（0.5 × 109个细胞/l）绝对中性粒细胞计数重建之间存在统计学意义（p = 0.03）。我们的结果还显示AML患者的KIR MSL值与cGvHD有很好的相关性（r = 0.9932）。结论：在选择相关供体阶段进行KIR/HLA I类分析对血液学移植的结果有影响，并可能减少并发症。
{"title":"The KIR/HLA class I co-expression and transplantation outcomes after HSCT/BMT from HLA-matched sibling donors","authors":"Joanna Dębska-Zielkowska , Bartosz Słomiński , Hanna Zielińska , Anna Dukat-Mazurek , Grażyna Moszkowska , Maria Bieniaszewska , Jan Maciej Zaucha , Piotr Trzonkowski , Maciej Zieliński","doi":"10.1016/j.trim.2025.102274","DOIUrl":"10.1016/j.trim.2025.102274","url":null,"abstract":"<div><h3>Background</h3><div>Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient.</div></div><div><h3>Methods</h3><div>We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [<em>n</em> = 24 with acute myeloid leukemia (AML), <em>n</em> = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and <em>n</em> = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors.</div></div><div><h3>Results</h3><div>Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD (<em>p</em> = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 × 10<sup>9</sup> cells/L) under 28 days (<em>p</em> = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients (<em>r</em> = 0.9932).</div></div><div><h3>Conclusion</h3><div>Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102274"},"PeriodicalIF":1.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795634","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 : 2025-08-05DOI: 10.1016/j.trim.2025.102277
Shaochen Yu , Mengjie Zhang , Ziyue Dou , Jian Lu
Posttransplantation rejection remains a critical challenge in organ transplantation. While immunosuppressants improve graft survival, their long-term side effects compromise patient quality of life, necessitating novel, side effect-free strategies to reduce the incidence of rejection. Regulatory B cells (Bregs), an immunomodulatory B lymphocyte subset within the immune microenvironment, have the potential to mitigate transplant rejection. However, Bregs alone are insufficient to control rejection, and their suppressive effects are notably limited in the absence of immunosuppression, highlighting their dependence on synergistic interactions with other regulatory mechanisms. This review summarizes the diverse phenotypes of Bregs and elucidates their immunomodulatory mechanisms, with a focus on cellular interactions (e.g., with Tregs, macrophages, dendritic cells, and NK cells) and cytokine secretion (e.g., IL-10, TGF-β, and IL-35). We critically evaluate animal and clinical trial data concerning the role of Bregs in transplantation, discussing their potential as therapeutic targets and the current limitations and future directions for harnessing Bregs to alleviate transplant rejection.
{"title":"Regulatory B cells: Synergistic cellular mechanisms and therapeutic potential for alleviating transplant rejection","authors":"Shaochen Yu , Mengjie Zhang , Ziyue Dou , Jian Lu","doi":"10.1016/j.trim.2025.102277","DOIUrl":"10.1016/j.trim.2025.102277","url":null,"abstract":"<div><div>Posttransplantation rejection remains a critical challenge in organ transplantation. While immunosuppressants improve graft survival, their long-term side effects compromise patient quality of life, necessitating novel, side effect-free strategies to reduce the incidence of rejection. Regulatory B cells (Bregs), an immunomodulatory B lymphocyte subset within the immune microenvironment, have the potential to mitigate transplant rejection. However, Bregs alone are insufficient to control rejection, and their suppressive effects are notably limited in the absence of immunosuppression, highlighting their dependence on synergistic interactions with other regulatory mechanisms. This review summarizes the diverse phenotypes of Bregs and elucidates their immunomodulatory mechanisms, with a focus on cellular interactions (e.g., with Tregs, macrophages, dendritic cells, and NK cells) and cytokine secretion (e.g., IL-10, TGF-β, and IL-35). We critically evaluate animal and clinical trial data concerning the role of Bregs in transplantation, discussing their potential as therapeutic targets and the current limitations and future directions for harnessing Bregs to alleviate transplant rejection.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102277"},"PeriodicalIF":1.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780156","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 : 2025-07-29DOI: 10.1016/j.trim.2025.102273
Roman Gorchs , Matt Stout , Brooke Cohen , Jaden Ju , Eileen Brewer , Nhu Thao Nguyen Galván , Abbas Rana
Background
Acute rejection in pediatric kidney transplant patients can increase posttransplant costs and lead to limited survival of the graft. Identifying key risk factors for acute rejection in pediatric kidney recipients may allow for physicians to better tailor immunosuppressant regimens and decrease the occurrence of acute rejection.
Methods
A retrospective analysis was performed using kidney transplantation data provided by the United Network for Organ Sharing (UNOS) for patients younger than 18 years old who received their first kidney transplant between January 2005 and December 2022. The resulting study population consisted of 10,126 patients over the 18-year span. Risk factors for acute rejection in the first year post-transplant were identified using a multivariate analysis.
Results
Several variables were found to be statistically significant risk factors for acute rejection, including donor age ≤ 10 (Odds Ratio 1.44), Obese BMI (BMI-for-age z-score > 2.0), (Odds Ratio 1.22), a 6 Human Leukocyte Antigen (HLA) mismatch (Odds Ratio 1.22) and recipient age between 15 and 18 (Odds Ratio 1.21). Multiple factors were found to be protective, including male sex (Odds Ratio 0.85) and recipient age between 5 and 10 (Odds Ratio 0.79).
Conclusions
The results indicate several significant risk factors such as the recipient age, Body Mass Index, sex and the number of HLA mismatches between the donor and the recipient. Physicians should consider these factors when personalizing immunosuppressive regimens for pediatric kidney transplant patients.
{"title":"Risk factors for acute rejection in pediatric kidney transplantation","authors":"Roman Gorchs , Matt Stout , Brooke Cohen , Jaden Ju , Eileen Brewer , Nhu Thao Nguyen Galván , Abbas Rana","doi":"10.1016/j.trim.2025.102273","DOIUrl":"10.1016/j.trim.2025.102273","url":null,"abstract":"<div><h3>Background</h3><div>Acute rejection in pediatric kidney transplant patients can increase posttransplant costs and lead to limited survival of the graft. Identifying key risk factors for acute rejection in pediatric kidney recipients may allow for physicians to better tailor immunosuppressant regimens and decrease the occurrence of acute rejection.</div></div><div><h3>Methods</h3><div>A retrospective analysis was performed using kidney transplantation data provided by the United Network for Organ Sharing (UNOS) for patients younger than 18 years old who received their first kidney transplant between January 2005 and December 2022. The resulting study population consisted of 10,126 patients over the 18-year span. Risk factors for acute rejection in the first year post-transplant were identified using a multivariate analysis.</div></div><div><h3>Results</h3><div>Several variables were found to be statistically significant risk factors for acute rejection, including donor age ≤ 10 (Odds Ratio 1.44), Obese BMI (BMI-for-age z-score > 2.0), (Odds Ratio 1.22), a 6 Human Leukocyte Antigen (HLA) mismatch (Odds Ratio 1.22) and recipient age between 15 and 18 (Odds Ratio 1.21). Multiple factors were found to be protective, including male sex (Odds Ratio 0.85) and recipient age between 5 and 10 (Odds Ratio 0.79).</div></div><div><h3>Conclusions</h3><div>The results indicate several significant risk factors such as the recipient age, Body Mass Index, sex and the number of HLA mismatches between the donor and the recipient. Physicians should consider these factors when personalizing immunosuppressive regimens for pediatric kidney transplant patients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102273"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761451","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 : 2025-07-29DOI: 10.1016/j.trim.2025.102272
Mani Ramzi , Mohammadnabi Sanaei , Maryam Hesamadini , Hossein Golmoghaddam , Mehdi Kalani , Nargess Arandi
Introduction
It has been proposed that regulatory T cells (Tregs) might be involved in the induction of transplantation tolerance after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the role of Treg subsets in allo-HSCT outcomes, including the development of acute graft-versus-host disease (aGVHD). Herein, we assessed for the first time the association between the frequency of regulatory T cell (Treg) subsets, including CD45RA+FOXP3low naïve (nTregs) and CD45RA−FOXP3high effector/memory Tregs (eTregs), and aGVHD occurrence during 90 days after allo-HSCT.
Methods
Twenty-four pairs of donors/recipients with hematologic malignancies who underwent HLA-matched allo-HSCT were enrolled. The frequencies of nTregs and eTregs were determined via four-color flow cytometry.
Results
Compared with non-aGVHD patients, aGVHD patients had a lower frequency of nTregs in their donors (*P = 0.016). The reconstitution rate of nTregs was significantly slower on day +60 post-allo-HSCT in aGVHD patients than in non-aGVHD patients (*P = 0.025).
Patients who received grafts with nTregs<0.19 and a median frequency of nTregs<0.13 and eTregs<0.58 on day +30 after transplantation presented a relatively high cumulative incidence of aGVHD (*P = 0.039, *P = 0.032, and *P = 0.036, respectively). Multivariate analysis revealed that a low median total number of Tregs recovered on days +30 and + 60 post-allo-HSCT was associated with an increased incidence of aGVHD [HR = 0.199, 95 % CI, 0.041–0.969; *P = 0.046 and HR = 0.092, 95 % CI, 0.011–0.765; *P = 0.026, respectively].
Conclusion
This study provides novel insights showing that high donor nTreg content and rapid recovery of nTregs and eTregs early on day 30 post-transplantation are closely linked to protection from aGVHD.
{"title":"The clinical significance of CD45RA+FOXP3low naïve and CD45RA−FOXP3high effector/memory Treg subsets in the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation","authors":"Mani Ramzi , Mohammadnabi Sanaei , Maryam Hesamadini , Hossein Golmoghaddam , Mehdi Kalani , Nargess Arandi","doi":"10.1016/j.trim.2025.102272","DOIUrl":"10.1016/j.trim.2025.102272","url":null,"abstract":"<div><h3>Introduction</h3><div>It has been proposed that regulatory T cells (Tregs) might be involved in the induction of transplantation tolerance after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the role of Treg subsets in allo-HSCT outcomes, including the development of acute graft-versus-host disease (aGVHD). Herein, we assessed for the first time the association between the frequency of regulatory T cell (Treg) subsets, including CD45RA<sup>+</sup>FOXP3<sup>low</sup> naïve (nTregs) and CD45RA<sup>−</sup>FOXP3<sup>high</sup> effector/memory Tregs (eTregs), and aGVHD occurrence during 90 days after allo-HSCT.</div></div><div><h3>Methods</h3><div>Twenty-four pairs of donors/recipients with hematologic malignancies who underwent HLA-matched allo-HSCT were enrolled. The frequencies of nTregs and eTregs were determined via four-color flow cytometry.</div></div><div><h3>Results</h3><div>Compared with non-aGVHD patients, aGVHD patients had a lower frequency of nTregs in their donors (*<em>P</em> = 0.016). The reconstitution rate of nTregs was significantly slower on day +60 post-allo-HSCT in aGVHD patients than in non-aGVHD patients (*<em>P</em> = 0.025).</div><div>Patients who received grafts with nTregs<0.19 and a median frequency of nTregs<0.13 and eTregs<0.58 on day +30 after transplantation presented a relatively high cumulative incidence of aGVHD (*<em>P</em> = 0.039, *<em>P</em> = 0.032, and *<em>P</em> = 0.036, respectively). Multivariate analysis revealed that a low median total number of Tregs recovered on days +30 and + 60 post-allo-HSCT was associated with an increased incidence of aGVHD [HR = 0.199, 95 % CI, 0.041–0.969; *<em>P</em> = 0.046 and HR = 0.092, 95 % CI, 0.011–0.765; *<em>P</em> = 0.026, respectively].</div></div><div><h3>Conclusion</h3><div>This study provides novel insights showing that high donor nTreg content and rapid recovery of nTregs and eTregs early on day 30 post-transplantation are closely linked to protection from aGVHD.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102272"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749571","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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