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}
Pub Date : 2025-07-29DOI: 10.1016/j.trim.2025.102270
Ananda Pipphali Vidya , Nicholas Jason Wijaya , Dhabitah Zahraa Puteri Gathmir , Naira Ayesha Kayla Kornel , Muhammad Farhan , Imelda Rosalyn Sianipar
Given the vulnerability of hematopoietic cell transplant (HCT) patients to influenza infection and its complications, annual vaccination is recommended. However, vaccination was known to be less effective in these patients. Multiple studies have assessed various effects in HCT recipients after receiving different vaccine doses. However, the results have been inconclusive. This meta-analysis aims to provide a comprehensive analysis of the effectiveness and safety of HCT recipients when they receive a higher and standard dose of influenza vaccines. This study used PRISMA guidelines on several databases until Oct 25, 2024. We used ROB 2.0 and Review Manager 5.4 Software for further analysis. We included four low-risk of bias studies, and we conducted further analysis. The efficacy of HAI titer 1:40, >4-fold, and confirmed influenza positives was comparable in both groups, with insignificant results in each follow-up group. However, the adverse effect was found significantly higher in the high-dose group, specifically the local adverse effect (p < 0.0001). High-dose influenza vaccines showed higher adverse events and more confirmed influenza cases than standard-dose, suggesting standard-dose may be preferable post-HCT. These findings underscore the need for further research, particularly in diverse populations and vulnerable groups.
{"title":"Safety and efficacy of high-dose versus standard-dose influenza vaccines in hematopoietic stem cell transplant recipients: A meta-analysis of randomized controlled trials","authors":"Ananda Pipphali Vidya , Nicholas Jason Wijaya , Dhabitah Zahraa Puteri Gathmir , Naira Ayesha Kayla Kornel , Muhammad Farhan , Imelda Rosalyn Sianipar","doi":"10.1016/j.trim.2025.102270","DOIUrl":"10.1016/j.trim.2025.102270","url":null,"abstract":"<div><div>Given the vulnerability of hematopoietic cell transplant (HCT) patients to influenza infection and its complications, annual vaccination is recommended. However, vaccination was known to be less effective in these patients. Multiple studies have assessed various effects in HCT recipients after receiving different vaccine doses. However, the results have been inconclusive. This meta-analysis aims to provide a comprehensive analysis of the effectiveness and safety of HCT recipients when they receive a higher and standard dose of influenza vaccines. This study used PRISMA guidelines on several databases until Oct 25, 2024. We used ROB 2.0 and Review Manager 5.4 Software for further analysis. We included four low-risk of bias studies, and we conducted further analysis. The efficacy of HAI titer <span><math><mo>≥</mo></math></span> 1:40, >4-fold, and confirmed influenza positives was comparable in both groups, with insignificant results in each follow-up group. However, the adverse effect was found significantly higher in the high-dose group, specifically the local adverse effect (<em>p</em> < 0.0001). High-dose influenza vaccines showed higher adverse events and more confirmed influenza cases than standard-dose, suggesting standard-dose may be preferable post-HCT. These findings underscore the need for further research, particularly in diverse populations and vulnerable groups.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102270"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749572","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.2025.102271
Xiaoli Lv , Huibo Li , Zhijian Li , Di Jin , Fei Leng , Jie Liu , Dan Guo , Shengjin Fan , Sheng Su
Background
Belumosudil is a selective ROCK2 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients who have failed at least two prior systemic therapies. By inhibiting ROCK2, Belumosudil can down-regulate the secretion of IL-21 and IL-17, and up-regulate regulatory T cells (Tregs), which serve to attenuate the inflammatory response. In addition, it can act as an antifibrotic by inhibiting the Rho-ROCK-MRTF pathway, as well as down-regulating the expression of pro-fibrotic genes and TGF-β signaling. Selective inhibition of ROCK2 also reduces M2-like macrophages and choroidal neovascularization, which further exerts antifibrotic effects. Therefore, belumosudil shows great potential in the treatment of chronic Graft-Versus-Host-Disease (cGVHD).
Case presentation
We report the clinical course of a 39-year-old man with severe progressive chronic ocular GVHD (oGVHD), who showed significant improvement in ocular surface damage, including damage to the cornea and meibomian glands, as well as dry eye symptoms, after oral administration of belumosudil. Corneal leukoplakia and neovascularization were significantly reduced after treatment. Moreover, the patient's ocular surface symptoms remained stable without deterioration after cataract surgery. The patient's quality of life was significantly enhanced.
Conclusion
We report the clinical outcomes of a patient with chronic oGVHD treated with belumosudil. The patient's clinical symptoms significantly improved, especially inflammation of the meibomian gland, corneal leukoplakia, and neovascularization. This highlights its application value in patients with cGVHD and provides a promising treatment option for patients with oGVHD.
背景：Belumosudil是美国食品和药物管理局（FDA）批准的一种选择性ROCK2抑制剂，用于治疗至少两次系统性治疗失败的患者。Belumosudil通过抑制ROCK2，下调IL-21和IL-17的分泌，上调调节性T细胞（regulatory T cells, Tregs），起到减轻炎症反应的作用。此外，它可以通过抑制Rho-ROCK-MRTF通路，下调促纤维化基因表达和TGF-β信号传导，起到抗纤维化的作用。选择性抑制ROCK2还可减少m2样巨噬细胞和脉络膜新生血管，从而进一步发挥抗纤维化作用。因此，白莫硫地尔在治疗慢性移植物抗宿主病（cGVHD）方面显示出巨大的潜力。病例介绍：我们报告了一名患有严重进行性慢性眼部GVHD （oGVHD）的39岁男性患者的临床过程，口服白莫舒地尔后，患者的眼表损伤，包括角膜和睑板腺的损伤以及干眼症状均有显著改善。治疗后角膜白斑和新生血管明显减少。此外，白内障手术后患者的眼表症状保持稳定，没有恶化。患者的生活质量明显提高。结论：我们报告了一例慢性oGVHD患者使用白莫硫地尔治疗的临床结果。患者的临床症状明显改善，尤其是睑板腺炎症、角膜白斑和新生血管。这突出了其在cGVHD患者中的应用价值，为oGVHD患者提供了一种有希望的治疗选择。
{"title":"Successful use of belumosudil in a patient with chronic ocular GVHD: A case report","authors":"Xiaoli Lv , Huibo Li , Zhijian Li , Di Jin , Fei Leng , Jie Liu , Dan Guo , Shengjin Fan , Sheng Su","doi":"10.1016/j.trim.2025.102271","DOIUrl":"10.1016/j.trim.2025.102271","url":null,"abstract":"<div><h3>Background</h3><div>Belumosudil is a selective ROCK2 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients who have failed at least two prior systemic therapies. By inhibiting ROCK2, Belumosudil can down-regulate the secretion of IL-21 and IL-17, and up-regulate regulatory T cells (Tregs), which serve to attenuate the inflammatory response. In addition, it can act as an antifibrotic by inhibiting the Rho-ROCK-MRTF pathway, as well as down-regulating the expression of pro-fibrotic genes and TGF-β signaling. Selective inhibition of ROCK2 also reduces M2-like macrophages and choroidal neovascularization, which further exerts antifibrotic effects. Therefore, belumosudil shows great potential in the treatment of chronic Graft-Versus-Host-Disease (cGVHD).</div></div><div><h3>Case presentation</h3><div>We report the clinical course of a 39-year-old man with severe progressive chronic ocular GVHD (oGVHD), who showed significant improvement in ocular surface damage, including damage to the cornea and meibomian glands, as well as dry eye symptoms, after oral administration of belumosudil. Corneal leukoplakia and neovascularization were significantly reduced after treatment. Moreover, the patient's ocular surface symptoms remained stable without deterioration after cataract surgery. The patient's quality of life was significantly enhanced.</div></div><div><h3>Conclusion</h3><div>We report the clinical outcomes of a patient with chronic oGVHD treated with belumosudil. The patient's clinical symptoms significantly improved, especially inflammation of the meibomian gland, corneal leukoplakia, and neovascularization. This highlights its application value in patients with cGVHD and provides a promising treatment option for patients with oGVHD.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102271"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761452","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 : 2025-07-22DOI: 10.1016/j.trim.2025.102264
Kyung-Hwa Shin , Soo Yong Lee , Min Ho Ju , Hyun-Ji Lee
Background
Sensitization of heart transplant (HT) recipients increases the risk of rejection. Assessment of sensitization using a calculated panel reactive antibody (cPRA) is crucial for evaluating transplant compatibility and predicting outcomes. This study investigated the impact of cPRA and pre-existing and de novo Human Leukocyte Antigen (HLA)-donor-specific antibodies (DSAs) on HT outcomes and aimed to identify recipients at a high risk of rejection.
Methods
This retrospective study included 121 adult recipients of HT from a single institution (2014–2023). cPRA values, flow cytometric crossmatches (FCXM), and DSAs were analyzed for their associations with antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR).
Results
Among the 121 HT recipients, 51.2 % experienced TCMR and 7.4 % experienced AMR. cPRA (I) ≥ 50 % was significantly associated with AMR, pre-existing DSA (pDSA), and positive FCXM. pDSA was present in 16.5 % of HT recipients and correlated with AMR but not mortality. De novo DSAs frequently emerged in 38 % of the recipients following TCMR episodes. Higher cPRA (I) levels correlated with increased rejection risk and shorter AMR-free survival.
Conclusions
High cPRA (≥50 %) significantly predicted the risk of AMR and correlated with pDSA and positive FCXM results. Pre-transplant cPRA assessment is crucial for identifying high-risk recipients and optimizing management strategies to improve HT outcomes.
{"title":"Pre-transplant sensitization and its effect on heart transplant rejection and survival outcomes","authors":"Kyung-Hwa Shin , Soo Yong Lee , Min Ho Ju , Hyun-Ji Lee","doi":"10.1016/j.trim.2025.102264","DOIUrl":"10.1016/j.trim.2025.102264","url":null,"abstract":"<div><h3>Background</h3><div>Sensitization of heart transplant (HT) recipients increases the risk of rejection. Assessment of sensitization using a calculated panel reactive antibody (cPRA) is crucial for evaluating transplant compatibility and predicting outcomes. This study investigated the impact of cPRA and pre-existing and <em>de novo</em> Human Leukocyte Antigen (HLA)-donor-specific antibodies (DSAs) on HT outcomes and aimed to identify recipients at a high risk of rejection.</div></div><div><h3>Methods</h3><div>This retrospective study included 121 adult recipients of HT from a single institution (2014–2023). cPRA values, flow cytometric crossmatches (FCXM), and DSAs were analyzed for their associations with antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR).</div></div><div><h3>Results</h3><div>Among the 121 HT recipients, 51.2 % experienced TCMR and 7.4 % experienced AMR. cPRA (I) ≥ 50 % was significantly associated with AMR, pre-existing DSA (pDSA), and positive FCXM. pDSA was present in 16.5 % of HT recipients and correlated with AMR but not mortality. <em>De novo</em> DSAs frequently emerged in 38 % of the recipients following TCMR episodes. Higher cPRA (I) levels correlated with increased rejection risk and shorter AMR-free survival.</div></div><div><h3>Conclusions</h3><div>High cPRA (≥50 %) significantly predicted the risk of AMR and correlated with pDSA and positive FCXM results. Pre-transplant cPRA assessment is crucial for identifying high-risk recipients and optimizing management strategies to improve HT outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102264"},"PeriodicalIF":1.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708968","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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