Pub Date : 2026-02-04DOI: 10.1016/j.trim.2026.102359
Yan Lv, Qi Wang, Ke Wang, Yixin Cai, Meijia Wang, Zhenli Huang, Ruijie Zhang, Junhui Wang, Suqin Xu, Huibo Shi, Huilan Zhang, Ni Zhang
Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory syndrome caused by mutations in the stimulator of interferon response cGAMP interactor 1 (STING1) gene, leading to lung and vascular injury. Most patients with SAVI develop disease in childhood or adolescence and rapidly progress to respiratory involvement, primarily interstitial pneumonia (IP) and/or pulmonary interstitial fibrosis (PIF), which may culminate in irreversible end-stage lung disease and respiratory failure. Currently, conventional medical treatments are controversial and challenging, with variable and generally unsatisfactory clinical efficacy. Lung transplantation (LT) remains the most effective strategy to prevent disease progression and improve respiratory function in patients with severe pulmonary involvement. We report in detail the clinical course of a 28-year-old adult patient with SAVI caused by a STING1 mutation, with adult-onset disease that rapidly progressed to severe lung injury requiring bilateral LT. Following transplantation, the patient experienced marked improvement of respiratory symptoms, including chest tightness, shortness of breath, and dyspnea, and was able to move freely without ventilator support.
{"title":"Bilateral lung transplantation for severe lung disease caused by a STING1 mutation: A case report.","authors":"Yan Lv, Qi Wang, Ke Wang, Yixin Cai, Meijia Wang, Zhenli Huang, Ruijie Zhang, Junhui Wang, Suqin Xu, Huibo Shi, Huilan Zhang, Ni Zhang","doi":"10.1016/j.trim.2026.102359","DOIUrl":"https://doi.org/10.1016/j.trim.2026.102359","url":null,"abstract":"<p><p>Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory syndrome caused by mutations in the stimulator of interferon response cGAMP interactor 1 (STING1) gene, leading to lung and vascular injury. Most patients with SAVI develop disease in childhood or adolescence and rapidly progress to respiratory involvement, primarily interstitial pneumonia (IP) and/or pulmonary interstitial fibrosis (PIF), which may culminate in irreversible end-stage lung disease and respiratory failure. Currently, conventional medical treatments are controversial and challenging, with variable and generally unsatisfactory clinical efficacy. Lung transplantation (LT) remains the most effective strategy to prevent disease progression and improve respiratory function in patients with severe pulmonary involvement. We report in detail the clinical course of a 28-year-old adult patient with SAVI caused by a STING1 mutation, with adult-onset disease that rapidly progressed to severe lung injury requiring bilateral LT. Following transplantation, the patient experienced marked improvement of respiratory symptoms, including chest tightness, shortness of breath, and dyspnea, and was able to move freely without ventilator support.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102359"},"PeriodicalIF":1.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132984","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}
Predicting the transplant outcome of Acute Lymphoblastic Leukemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a challenge. It is necessary to have prognostic biomarkers that can be monitored in these patients. In the present single center, long term follow-up study, immune cell composition or the immunophenotype of Acute Lymphoblastic Leukemia patients (n = 14) was analyzed at various intervals following allogeneic HSCT and correlated with clinical outcomes. Long-term survivors post-HSCT showed distinct immune cell profiles compared to non-survivors. Long term survivors exhibited higher expression of Vδ2+CD69+ (p = 0.0126), and Vδ1+CD16b+ T cells (p = 0.0485) at baseline, compared to non-survivors. The analysis of donor immune cell composition showed difference at baseline, donors with higher levels of NKT+ cells and lower Vδ1+perforin+ T cells led to longer survival of respective recipients. Earlier WBC engraftment and incidence of chronic GVHD were other independent clinical factors associated with higher overall survival post- allogeneic HSCT. Furthermore, donors with higher baseline percentages of γδ T cells, CD19+ B cells, CD4 T cells, Vδ2 Naïve, Vδ2 TemRA, CD3+CD25+, and Vδ2+CD25+; and low Effector Memory CD3+ and Vδ1+ T cells were associated with fewer Cytomegalovirus (CMV) reactivation in their recipients. The present study underscores the importance of compositional analysis of immune cells in both recipients and donors as a discerning predictive tool for anticipating long-term clinical outcomes following allogeneic HSCT and highlights the need for future validation in larger cohorts.
{"title":"Gamma delta T cell reconstitution in Acute Lymphoblastic Leukemia patients post allogeneic HSCT predicts clinical outcome and overall survival.","authors":"Gauri Mirji, Sachin Punatar, Navin Khattry, Shubhada Chiplunkar","doi":"10.1016/j.trim.2026.102358","DOIUrl":"10.1016/j.trim.2026.102358","url":null,"abstract":"<p><p>Predicting the transplant outcome of Acute Lymphoblastic Leukemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a challenge. It is necessary to have prognostic biomarkers that can be monitored in these patients. In the present single center, long term follow-up study, immune cell composition or the immunophenotype of Acute Lymphoblastic Leukemia patients (n = 14) was analyzed at various intervals following allogeneic HSCT and correlated with clinical outcomes. Long-term survivors post-HSCT showed distinct immune cell profiles compared to non-survivors. Long term survivors exhibited higher expression of Vδ2<sup>+</sup>CD69<sup>+</sup> (p = 0.0126), and Vδ1<sup>+</sup>CD16b<sup>+</sup> T cells (p = 0.0485) at baseline, compared to non-survivors. The analysis of donor immune cell composition showed difference at baseline, donors with higher levels of NKT<sup>+</sup> cells and lower Vδ1<sup>+</sup>perforin<sup>+</sup> T cells led to longer survival of respective recipients. Earlier WBC engraftment and incidence of chronic GVHD were other independent clinical factors associated with higher overall survival post- allogeneic HSCT. Furthermore, donors with higher baseline percentages of γδ T cells, CD19<sup>+</sup> B cells, CD4 T cells, Vδ2 Naïve, Vδ2 TemRA, CD3<sup>+</sup>CD25<sup>+</sup>, and Vδ2<sup>+</sup>CD25<sup>+</sup>; and low Effector Memory CD3<sup>+</sup> and Vδ1<sup>+</sup> T cells were associated with fewer Cytomegalovirus (CMV) reactivation in their recipients. The present study underscores the importance of compositional analysis of immune cells in both recipients and donors as a discerning predictive tool for anticipating long-term clinical outcomes following allogeneic HSCT and highlights the need for future validation in larger cohorts.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102358"},"PeriodicalIF":1.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1016/j.trim.2026.102360
Min Min, Jiyuan Wang, Xiao Fang, Yu Chen, Yawei Wang
Ischemia is a common clinical condition, characterized by reduced blood supply to tissues or organs owing to blockage or constriction of blood vessels. In this study, we hypothesized that the humoral immune response is activated by ischemia-related neoepitopes. Upon detection of these newly exposed or modified antigens, the immune system mounts a humoral response involving the production of specific antibodies. These antibodies may then contribute to amplification of the inflammatory cascade, ultimately exacerbating tissue damage during secondary ischemia-reperfusion (I/R) injury in mice. To test this hypothesis, we conducted a series of experiments using a well-established murine model of two sequential I/R injuries. Our findings indicated that the presence of these neoepitopes was associated with the formation of germinal center B cells and subsequent immunoglobulin isotype switching. Consequently, mice exhibited more severe tissue injury during the secondary I/R event, as demonstrated by greater histopathological damage and elevated serum enzyme levels (p < 0.05). Furthermore, administration of tacrolimus following the first I/R injury significantly attenuated secondary injury, reducing its severity to a level comparable to that observed during the primary event (p < 0.05). This intervention was also associated with a marked decrease in IgG and complement C4d deposition within the affected kidney (∼50% reduction). Collectively, these findings indicate the presence of neoepitopes and the humoral immune response they elicit, offering insights into the development of novel clinical interventions.
{"title":"Exposure to ischemia-related neoepitopes exacerbates secondary ischemia-reperfusion injury in mice.","authors":"Min Min, Jiyuan Wang, Xiao Fang, Yu Chen, Yawei Wang","doi":"10.1016/j.trim.2026.102360","DOIUrl":"10.1016/j.trim.2026.102360","url":null,"abstract":"<p><p>Ischemia is a common clinical condition, characterized by reduced blood supply to tissues or organs owing to blockage or constriction of blood vessels. In this study, we hypothesized that the humoral immune response is activated by ischemia-related neoepitopes. Upon detection of these newly exposed or modified antigens, the immune system mounts a humoral response involving the production of specific antibodies. These antibodies may then contribute to amplification of the inflammatory cascade, ultimately exacerbating tissue damage during secondary ischemia-reperfusion (I/R) injury in mice. To test this hypothesis, we conducted a series of experiments using a well-established murine model of two sequential I/R injuries. Our findings indicated that the presence of these neoepitopes was associated with the formation of germinal center B cells and subsequent immunoglobulin isotype switching. Consequently, mice exhibited more severe tissue injury during the secondary I/R event, as demonstrated by greater histopathological damage and elevated serum enzyme levels (p < 0.05). Furthermore, administration of tacrolimus following the first I/R injury significantly attenuated secondary injury, reducing its severity to a level comparable to that observed during the primary event (p < 0.05). This intervention was also associated with a marked decrease in IgG and complement C4d deposition within the affected kidney (∼50% reduction). Collectively, these findings indicate the presence of neoepitopes and the humoral immune response they elicit, offering insights into the development of novel clinical interventions.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102360"},"PeriodicalIF":1.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133003","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 : 2026-01-19DOI: 10.1016/j.trim.2026.102349
Tauana Freitas Casagrande , Heloisa Cristina Caldas , Pedro Henrique Fogaça Jordão , Fernanda Salomão Gorayeb-Polacchini , Gabriel Ribeiro Ramos , Ida Maria Maximina Fernandes-Charpiot , Mario Abbud-Filho
Background
Cytomegalovirus (CMV) infection remains a major complication in kidney transplant recipients (KTRs), particularly among donor-negative/recipient-positive (D−/R+) individuals, who are at intermediate risk for viral reactivation. Although CMV DNAemia monitoring allows for preemptive therapy, the optimal threshold to predict disease remains uncertain. This study aimed to determine a clinically relevant CMV DNAemia cut-off for predicting CMV disease in D−/R+ KTRs and evaluate associated clinical outcomes.
Methods
A retrospective cohort of 192 D−/R+ KTRs was followed for one year post-transplantation. Patients were stratified by peak CMV DNAemia levels. Clinical, laboratory, and graft-related outcomes were assessed. Logistic regression identified independent predictors of CMV disease. Receiver operating characteristic (ROC) analysis determined the optimal DNAemia threshold.
Results
CMV DNAemia ≥1001 IU/mL occurred in 71% of patients and was associated with earlier infection onset, higher peak viral loads, increased use of thymoglobulin, and prolonged delayed graft function (DGF). CMV disease developed in 15% of patients and was independently associated with Kidney Donor Profile Index (KDPI) >80%, elevated DNAemia, longer DGF, lymphopenia, thrombocytopenia, graft loss, and acute rejection. A DNAemia threshold of 14,200 IU/mL (log > 4.15) predicted CMV disease with 63.1% sensitivity and 66.0% specificity (AUC = 0.62). Moreover, recipients of high-KDPI grafts had higher rates of CMV recurrence and peak DNAemia.
Conclusions
Elevated CMV DNAemia, poor donor organ quality, and prolonged DGF are key predictors of CMV disease in D−/R+ KTRs. A DNAemia threshold >14,200 IU/mL was associated with an increased risk of CMV disease and may support risk stratification within preemptive management strategies in this intermediate-risk group.
{"title":"Accurate prediction of cytomegalovirus disease through optimized viral load cut-offs in intermediate-risk kidney transplant recipients","authors":"Tauana Freitas Casagrande , Heloisa Cristina Caldas , Pedro Henrique Fogaça Jordão , Fernanda Salomão Gorayeb-Polacchini , Gabriel Ribeiro Ramos , Ida Maria Maximina Fernandes-Charpiot , Mario Abbud-Filho","doi":"10.1016/j.trim.2026.102349","DOIUrl":"10.1016/j.trim.2026.102349","url":null,"abstract":"<div><h3>Background</h3><div>Cytomegalovirus (CMV) infection remains a major complication in kidney transplant recipients (KTRs), particularly among donor-negative/recipient-positive (D−/R+) individuals, who are at intermediate risk for viral reactivation. Although CMV DNAemia monitoring allows for preemptive therapy, the optimal threshold to predict disease remains uncertain. This study aimed to determine a clinically relevant CMV DNAemia cut-off for predicting CMV disease in D−/R+ KTRs and evaluate associated clinical outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort of 192 D−/R+ KTRs was followed for one year post-transplantation. Patients were stratified by peak CMV DNAemia levels. Clinical, laboratory, and graft-related outcomes were assessed. Logistic regression identified independent predictors of CMV disease. Receiver operating characteristic (ROC) analysis determined the optimal DNAemia threshold.</div></div><div><h3>Results</h3><div>CMV DNAemia ≥1001 IU/mL occurred in 71% of patients and was associated with earlier infection onset, higher peak viral loads, increased use of thymoglobulin, and prolonged delayed graft function (DGF). CMV disease developed in 15% of patients and was independently associated with Kidney Donor Profile Index (KDPI) >80%, elevated DNAemia, longer DGF, lymphopenia, thrombocytopenia, graft loss, and acute rejection. A DNAemia threshold of 14,200 IU/mL (log > 4.15) predicted CMV disease with 63.1% sensitivity and 66.0% specificity (AUC = 0.62). Moreover, recipients of high-KDPI grafts had higher rates of CMV recurrence and peak DNAemia.</div></div><div><h3>Conclusions</h3><div>Elevated CMV DNAemia, poor donor organ quality, and prolonged DGF are key predictors of CMV disease in D−/R+ KTRs. A DNAemia threshold >14,200 IU/mL was associated with an increased risk of CMV disease and may support risk stratification within preemptive management strategies in this intermediate-risk group.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"95 ","pages":"Article 102349"},"PeriodicalIF":1.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146006521","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 : 2026-01-10DOI: 10.1016/j.trim.2026.102347
Ewa Bembnista , Paula Matuszak , Anna Łojko-Dankowska , Dominik Dytfeld , Magdalena Matuszak , Anna Wache , Katarzyna Kaźmierska , Andrzej Szczepaniak , Bartosz Małecki , Patrycja Stawicka , Joanna Kujawska , Anna Płotka , Anna Hoppe , Justyna Marcinkowska , Kinga Eling , Krzysztof Lewandowski , Lidia Gil
Allogeneic hematopoietic stem cell (allo-HSC) transplantation (allo-HSCT) is a therapy of choice for patients requiring total bone marrow replacement. One of the critical issues is optimizing the number of allo-HSCs for successful outcomes, measured by the engraftment time and the incidence/severity of graft versus host disease (GvHD). We evaluated engraftment time and GvHD in comparison to the composition of infused CD34+ immature HSCs and CD3+ T cells in all-HSCTs. The study evaluated 97 patients with allo-HSCT from matched related (group MRD; n = 40), matched unrelated (group MUD; n = 28), mismatched unrelated (group MMUD; n = 6), and haploidentical (group haplo; n = 23) donors. Overall, we did not observe any correlation between the total count of CD34+ allo-HSC and CD3+ T cells or the count of CD34+ and CD3+ calculated per kilogram of body weight (kg) on engraftment as well as GvHD symptoms in all studied groups. However, the CD34+/CD3+ ratio may provide valuable information in the process of a graft quality assessment in haploidentical allo-HCST for the choice of therapeutic options.
{"title":"CD34+/CD3+ cells ratio in the peripheral blood stem cells product and graft-versus-host disease: Is there still room for improvement?","authors":"Ewa Bembnista , Paula Matuszak , Anna Łojko-Dankowska , Dominik Dytfeld , Magdalena Matuszak , Anna Wache , Katarzyna Kaźmierska , Andrzej Szczepaniak , Bartosz Małecki , Patrycja Stawicka , Joanna Kujawska , Anna Płotka , Anna Hoppe , Justyna Marcinkowska , Kinga Eling , Krzysztof Lewandowski , Lidia Gil","doi":"10.1016/j.trim.2026.102347","DOIUrl":"10.1016/j.trim.2026.102347","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell (allo-HSC) transplantation (allo-HSCT) is a therapy of choice for patients requiring total bone marrow replacement. One of the critical issues is optimizing the number of allo-HSCs for successful outcomes, measured by the engraftment time and the incidence/severity of graft versus host disease (GvHD). We evaluated engraftment time and GvHD in comparison to the composition of infused CD34+ immature HSCs and CD3+ T cells in all-HSCTs. The study evaluated 97 patients with allo-HSCT from matched related (group MRD; <em>n</em> = 40), matched unrelated (group MUD; <em>n</em> = 28), mismatched unrelated (group MMUD; <em>n</em> = 6), and haploidentical (group haplo; <em>n</em> = 23) donors. Overall, we did not observe any correlation between the total count of CD34+ allo-HSC and CD3+ T cells or the count of CD34+ and CD3+ calculated per kilogram of body weight (kg) on engraftment as well as GvHD symptoms in all studied groups. However, the CD34+/CD3+ ratio may provide valuable information in the process of a graft quality assessment in haploidentical allo-HCST for the choice of therapeutic options.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102347"},"PeriodicalIF":1.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 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}
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