Pub Date : 2025-05-31DOI: 10.1016/j.trim.2025.102245
Andrea Zajacova , Majd Alkhouri , Goncalo Ferrao , Miray Guney , David Rezac , Kristyna Vyskocilova , Tereza Kotowski , Alzbeta Dutkova , Eliska Dvorackova , Robert Lischke , Libor Fila , David J. Ross , Bart Vanaudenaerde , Jan Havlin
Background
Baseline lung allograft dysfunction (BLAD) is defined as the failure to achieve normal pulmonary function—specifically, forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) values of ≥80 %—within the first year after lung transplantation. It is hypothesised that early subclinical injury, reflected by elevated donor-derived cell-free DNA (dd-cfDNA), both in absolute concentration and percentage (dd-cfDNA%), as well as total cell-free DNA (cfDNA), may be predictive of subsequent BLAD development.
Methods
We included patients who underwent bilateral lung transplantation between May 2021 and September 2023. Blood samples collected between 3 and 9 months post-transplantation were analysed for dd-cfDNA%, dd-cfDNA concentration (copies/mL), and estimated total cfDNA (copies/mL). BLAD was defined by failure to achieve both FEV₁ and FVC ≥80 % of predicted values within the first year.
Results
A total of 158 samples from 37 patients were analysed. Ten patients (27 %) met the BLAD criteria. Those with BLAD had significantly higher dd-cfDNA levels (median: 39 cp/mL) compared to non-BLAD patients (26 cp/mL; p = 0.01). Similarly, total cfDNA levels were significantly elevated in the BLAD group (22,809 cp/mL vs. 13,840 cp/mL; p = 0.002). However, dd-cfDNA% did not differ significantly (0.23 % vs. 0.15 %; p = 0.2).
Conclusion
Elevated absolute dd-cfDNA and total cfDNA levels in the early post-transplant period were associated with BLAD, suggesting that cfDNA may serve as a potential predictive biomarker. These findings support the potential of cfDNA-based biomarkers to enhance early detection of graft dysfunction, warranting validation in larger cohorts.
{"title":"Early post-lung transplant cell-free DNA levels are associated with baseline lung allograft function","authors":"Andrea Zajacova , Majd Alkhouri , Goncalo Ferrao , Miray Guney , David Rezac , Kristyna Vyskocilova , Tereza Kotowski , Alzbeta Dutkova , Eliska Dvorackova , Robert Lischke , Libor Fila , David J. Ross , Bart Vanaudenaerde , Jan Havlin","doi":"10.1016/j.trim.2025.102245","DOIUrl":"10.1016/j.trim.2025.102245","url":null,"abstract":"<div><h3>Background</h3><div>Baseline lung allograft dysfunction (BLAD) is defined as the failure to achieve normal pulmonary function—specifically, forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) values of ≥80 %—within the first year after lung transplantation. It is hypothesised that early subclinical injury, reflected by elevated donor-derived cell-free DNA (dd-cfDNA), both in absolute concentration and percentage (dd-cfDNA%), as well as total cell-free DNA (cfDNA), may be predictive of subsequent BLAD development.</div></div><div><h3>Methods</h3><div>We included patients who underwent bilateral lung transplantation between May 2021 and September 2023. Blood samples collected between 3 and 9 months post-transplantation were analysed for dd-cfDNA%, dd-cfDNA concentration (copies/mL), and estimated total cfDNA (copies/mL). BLAD was defined by failure to achieve both FEV₁ and FVC ≥80 % of predicted values within the first year.</div></div><div><h3>Results</h3><div>A total of 158 samples from 37 patients were analysed. Ten patients (27 %) met the BLAD criteria. Those with BLAD had significantly higher dd-cfDNA levels (median: 39 cp/mL) compared to non-BLAD patients (26 cp/mL; <em>p</em> = 0.01). Similarly, total cfDNA levels were significantly elevated in the BLAD group (22,809 cp/mL vs. 13,840 cp/mL; <em>p</em> = 0.002). However, dd-cfDNA% did not differ significantly (0.23 % vs. 0.15 %; <em>p</em> = 0.2).</div></div><div><h3>Conclusion</h3><div>Elevated absolute dd-cfDNA and total cfDNA levels in the early post-transplant period were associated with BLAD, suggesting that cfDNA may serve as a potential predictive biomarker. These findings support the potential of cfDNA-based biomarkers to enhance early detection of graft dysfunction, warranting validation in larger cohorts.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102245"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209628","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 : 2025-05-23DOI: 10.1016/j.trim.2025.102244
Xi Lu , Yu-di Han , Xiao-ran Zu , Jin-can Huang , Li Li , Meng Wang , Yu-Ting Wang , Ling-li Guo , Lin Zhou , Yan Han
Skin allografts are prone to rejection because of their high immunogenicity. By achieving immune tolerance, the long-term survival of skin allografts can be extended without the need for immunosuppressants or with only short-term low-dose dependency. Tolerogenic dendritic cells (tolDCs) show a strong potential for graft tolerance. We explored the mechanism whereby rapamycin-modified CD169low/-tolDCs regulate interleukin-10 (IL-10) B regulatory (IL-10+ Breg) cell production and mediate the long-term survival of skin allografts in mice. CD169low/-tolDCs were obtained through flow cytometry sorting after treating the mesenchymal stem cell (MSC)-derived dendritic cells with a low dose of GM-CSF. A treatment regimen combining preoperative stimulation and postoperative adoptive infusion of CD169low/-tolDCs was used to treat an acute rejection (AR) mouse skin transplantation model—the adoptive infusion group. An equivalent dose of saline was administered to the control group. Survival and graft rejection rates were assessed. Mixed lymphocyte culture, flow cytometry, immunohistochemistry (IHC), and western blotting (WB) were used to elucidate the expression of different IL-10+ Breg subsets in mice treated with adoptive infusion therapy and the molecular mechanisms whereby CD169low/-tolDCs induce IL-10+ Breg production to mediate tolerance. Adoptive infusion of CD169low/−tol DCs markedly prolonged the rejection time after skin transplantation in mice and promoted graft survival. A significant increase was observed in local blood flow signals in the transplanted skin, along with mild local inflammation. Flow cytometric analysis revealed a positive correlation between high expression of IL-10+ Breg and the changes in Foxp3+ Tregs in vivo, primarily enriched in the CD19 + CD24 + CD27+ mBreg and CD19 + CD23 + CD27-CD24+ Breg subsets, with higher levels of IgM expression. Significant differences were observed compared with control mice. CD79b/NF-κB pathway was found to be involved in Breg production. CD24, CD23, CD79, BTK, NF-κB p50/p65, CD40, and IKKα levels in the adoptive infusion group were significantly increased compared with those in the control group. Adoptive infusion of CD169low/-MSCs/tolDCs may activate the NF-κB pathway through CD79/BTK-dependent and CD40/IKKα-independent pathways, inducing high expression of IL-10 + Breg and promoting graft survival of mouse skin transplantation.
{"title":"Rapamycin-modified CD169low/-tolDC promotes skin graft survival in mice via IL-10+Breg","authors":"Xi Lu , Yu-di Han , Xiao-ran Zu , Jin-can Huang , Li Li , Meng Wang , Yu-Ting Wang , Ling-li Guo , Lin Zhou , Yan Han","doi":"10.1016/j.trim.2025.102244","DOIUrl":"10.1016/j.trim.2025.102244","url":null,"abstract":"<div><div>Skin allografts are prone to rejection because of their high immunogenicity. By achieving immune tolerance, the long-term survival of skin allografts can be extended without the need for immunosuppressants or with only short-term low-dose dependency. Tolerogenic dendritic cells (tolDCs) show a strong potential for graft tolerance. We explored the mechanism whereby rapamycin-modified CD169low/-tolDCs regulate interleukin-10 (IL-10) B regulatory (IL-10+ Breg) cell production and mediate the long-term survival of skin allografts in mice. CD169low/-tolDCs were obtained through flow cytometry sorting after treating the mesenchymal stem cell (MSC)-derived dendritic cells with a low dose of GM-CSF. A treatment regimen combining preoperative stimulation and postoperative adoptive infusion of CD169low/-tolDCs was used to treat an acute rejection (AR) mouse skin transplantation model—the adoptive infusion group. An equivalent dose of saline was administered to the control group. Survival and graft rejection rates were assessed. Mixed lymphocyte culture, flow cytometry, immunohistochemistry (IHC), and western blotting (WB) were used to elucidate the expression of different IL-10+ Breg subsets in mice treated with adoptive infusion therapy and the molecular mechanisms whereby CD169low/-tolDCs induce IL-10+ Breg production to mediate tolerance. Adoptive infusion of CD169low/−tol DCs markedly prolonged the rejection time after skin transplantation in mice and promoted graft survival. A significant increase was observed in local blood flow signals in the transplanted skin, along with mild local inflammation. Flow cytometric analysis revealed a positive correlation between high expression of IL-10+ Breg and the changes in Foxp3+ Tregs in vivo, primarily enriched in the CD19 + CD24 + CD27+ mBreg and CD19 + CD23 + CD27-CD24+ Breg subsets, with higher levels of IgM expression. Significant differences were observed compared with control mice. CD79b/NF-κB pathway was found to be involved in Breg production. CD24, CD23, CD79, BTK, NF-κB p50/p65, CD40, and IKKα levels in the adoptive infusion group were significantly increased compared with those in the control group. Adoptive infusion of CD169low/-MSCs/tolDCs may activate the NF-κB pathway through CD79/BTK-dependent and CD40/IKKα-independent pathways, inducing high expression of IL-10 + Breg and promoting graft survival of mouse skin transplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102244"},"PeriodicalIF":1.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143617","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 : 2025-05-22DOI: 10.1016/j.trim.2025.102242
Elena-Bianca Barbir , Abdullah Jalal , Joseph Grande , Svetomir N. Markovic , Aleksandra Kukla , Itunu Owoyemi
The widespread use of immunotherapy in the management of cancers has led to improved overall survival and progression free survival. Due to increased risk of allograft rejection, organ transplant recipients are often excluded in clinical trials or offered immunotherapy only as salvage therapy. We report a case of successful use of Cemiplimab, an immune checkpoint inhibitor, in a high immunologic risk kidney transplant recipient who was diagnosed with metastatic squamous cell carcinoma (SCC) twenty-five months post-transplant. He started Cemiplimab five months post diagnosis of SCC, as third line therapy, after demonstrating progression of metastatic skull-based disease on prior lines of therapy. His maintenance immunosuppression was changed from triple immunosuppression with tacrolimus, mycophenolate and prednisone to sirolimus with a high trough target of 10–15 ng/mL and steroid therapy. He tolerated the high sirolimus trough and continued on Cemiplimab for six months with clinically stable allograft function and a good quality of life. Notably, he demonstrated response of his previously chemotherapy refractory metastatic disease. He passed away from radiation necrosis of the brain at sixty-eight months post-transplant.
{"title":"Successful use of cemiplimab in a high immunologic risk kidney transplant recipient with metastatic squamous cell carcinoma","authors":"Elena-Bianca Barbir , Abdullah Jalal , Joseph Grande , Svetomir N. Markovic , Aleksandra Kukla , Itunu Owoyemi","doi":"10.1016/j.trim.2025.102242","DOIUrl":"10.1016/j.trim.2025.102242","url":null,"abstract":"<div><div>The widespread use of immunotherapy in the management of cancers has led to improved overall survival and progression free survival. Due to increased risk of allograft rejection, organ transplant recipients are often excluded in clinical trials or offered immunotherapy only as salvage therapy. We report a case of successful use of Cemiplimab, an immune checkpoint inhibitor, in a high immunologic risk kidney transplant recipient who was diagnosed with metastatic squamous cell carcinoma (SCC) twenty-five months post-transplant. He started Cemiplimab five months post diagnosis of SCC, as third line therapy, after demonstrating progression of metastatic skull-based disease on prior lines of therapy. His maintenance immunosuppression was changed from triple immunosuppression with tacrolimus, mycophenolate and prednisone to sirolimus with a high trough target of 10–15 ng/mL and steroid therapy. He tolerated the high sirolimus trough and continued on Cemiplimab for six months with clinically stable allograft function and a good quality of life. Notably, he demonstrated response of his previously chemotherapy refractory metastatic disease. He passed away from radiation necrosis of the brain at sixty-eight months post-transplant.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102242"},"PeriodicalIF":1.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143624","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 : 2025-05-19DOI: 10.1016/j.trim.2025.102243
Fatemeh Gabeleh , Mohammad Mahdavi , Mohammad Hadi Karbalaie Niya , Mehri Amiri , Mehrdad Ravanshad
Background
The Administration of anti-rejection medications in solid organ recipients may increase the risk of acquiring multiple infections. This study aimed to diagnose and monitor BKV and JCV viral infections in pediatric heart transplant recipients.
Methods
A cohort of 28 children, all under 18 years old, undergoing heart transplants was studied. Plasma and urine samples were collected, followed by DNA extraction and molecular testing to quantify viral loads. Demographic and clinical information were recorded and analyzed.
Results
The BK and JC viruria frequency among the cohort was 41.7 % and 12.5 %, respectively. No instances of BKV and JCV viremia were detected. The BKV DNA viral loads ranged from 3.1 × 102 to 11.8 × 106 copies/mL, while the JC viruria viral load ranged from 1.1 × 102 to 13.6 × 106 copies/mL. BKV-JCV co-infection was identified in 12.5 % of patients.
Conclusions
Considering a high prevalence of BKV viruria in the recruited patients, clinicians should be well acquainted with the steps involved in the diagnosis and management of polyomaviral infections.
{"title":"Survey of prevalence of BKV and JCV infections in pediatric heart transplant recipients","authors":"Fatemeh Gabeleh , Mohammad Mahdavi , Mohammad Hadi Karbalaie Niya , Mehri Amiri , Mehrdad Ravanshad","doi":"10.1016/j.trim.2025.102243","DOIUrl":"10.1016/j.trim.2025.102243","url":null,"abstract":"<div><h3>Background</h3><div>The Administration of anti-rejection medications in solid organ recipients may increase the risk of acquiring multiple infections. This study aimed to diagnose and monitor BKV and JCV viral infections in pediatric heart transplant recipients.</div></div><div><h3>Methods</h3><div>A cohort of 28 children, all under 18 years old, undergoing heart transplants was studied. Plasma and urine samples were collected, followed by DNA extraction and molecular testing to quantify viral loads. Demographic and clinical information were recorded and analyzed.</div></div><div><h3>Results</h3><div>The BK and JC viruria frequency among the cohort was 41.7 % and 12.5 %, respectively. No instances of BKV and JCV viremia were detected. The BKV DNA viral loads ranged from 3.1 × 10<sup>2</sup> to 11.8 × 10<sup>6</sup> copies/mL, while the JC viruria viral load ranged from 1.1 × 10<sup>2</sup> to 13.6 × 10<sup>6</sup> copies/mL. BKV-JCV co-infection was identified in 12.5 % of patients.</div></div><div><h3>Conclusions</h3><div>Considering a high prevalence of BKV viruria in the recruited patients, clinicians should be well acquainted with the steps involved in the diagnosis and management of polyomaviral infections.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102243"},"PeriodicalIF":1.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120941","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 : 2025-05-13DOI: 10.1016/j.trim.2025.102241
Meng Lu , Jia-yan Leng , Chen-yun Xu , Chao-ran Lv , Zhen Qian , Yan Zhou , Di Yu , Jun Qian
To overcome the cell-dose barrier of cord blood, double unrelated umbilical cord blood transplantation (UCBT) has become increasingly common in adults with severe aplastic anemia (SAA). Pre-existing donor-specific anti-HLA antibodies (DSAs) represent a risk factor for graft failure (GF). Desensitization therapy should be conducted to reduce circulating DSA levels, thereby decreasing the risk of GF. This report details a case of a female patient with acquired SAA and pre-transplantation anti-HLA antibodies. Desensitization with rituximab, intravenous immunoglobulin (IVIG), and plasma exchange (PE) was performed before transplantation with a conditioning regimen of fludarabine (30 mg/m2 for six days) and cyclophosphamide (50 mg/kg/d for four days). DSA titers were significantly reduced; the patient was successfully treated with double unrelated UCBT. Currently, complete remission (CR) status has been maintained for over a year after UCBT, with no signs of graft-vs-host disease. Our findings support the use of double-unit unrelated UCBT in adult patients with SAA when cell doses of single-unit UCB are inadequate. Monitoring and reducing DSA levels before and after UCBT is an efficient way to reduce the risk of GF.
{"title":"Successful treatment of very severe aplastic anemia with double unrelated umbilical cord blood transplantation in a donor-specific antigen positive adult patient: A case report and review","authors":"Meng Lu , Jia-yan Leng , Chen-yun Xu , Chao-ran Lv , Zhen Qian , Yan Zhou , Di Yu , Jun Qian","doi":"10.1016/j.trim.2025.102241","DOIUrl":"10.1016/j.trim.2025.102241","url":null,"abstract":"<div><div>To overcome the cell-dose barrier of cord blood, double unrelated umbilical cord blood transplantation (UCBT) has become increasingly common in adults with severe aplastic anemia (SAA). Pre-existing donor-specific anti-HLA antibodies (DSAs) represent a risk factor for graft failure (GF). Desensitization therapy should be conducted to reduce circulating DSA levels, thereby decreasing the risk of GF. This report details a case of a female patient with acquired SAA and pre-transplantation anti-HLA antibodies. Desensitization with rituximab, intravenous immunoglobulin (IVIG), and plasma exchange (PE) was performed before transplantation with a conditioning regimen of fludarabine (30 mg/m<sup>2</sup> for six days) and cyclophosphamide (50 mg/kg/d for four days). DSA titers were significantly reduced; the patient was successfully treated with double unrelated UCBT. Currently, complete remission (CR) status has been maintained for over a year after UCBT, with no signs of graft-vs-host disease. Our findings support the use of double-unit unrelated UCBT in adult patients with SAA when cell doses of single-unit UCB are inadequate. Monitoring and reducing DSA levels before and after UCBT is an efficient way to reduce the risk of GF.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102241"},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080299","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 : 2025-05-08DOI: 10.1016/j.trim.2025.102231
Ehsan Yazdandoust , Abbas Hajifathali , Amir Teimourpour , Sedigheh Amini-Kafiabad , Elham Roshandel
Background
ABO blood group mismatch between donor and recipients is not considered as a major contraindication to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, there is still conflicting reports on the impact of ABO incompatibility on allo-HSCT outcomes, including the risk of graft-versus-host disease (GVHD), relapse of underlying disease, and patient survivals.
Methods
We conducted a retrospective cohort study in 157 patients who underwent HSCT from October 1st 2019, to September 30th 2023, to determine the effect of ABO compatibility on allo-HSCT outcomes, as evaluating for pure red cell aplasia, engraftment time/status, chronic/acute allo-GVHD, and non-relapse mortality.
Results
Overall, 50.3 % of HSCT patients were ABO incompatible and 49.7 % of allo-HSCT patients were ABO compatible. Our findings suggest that the risk of pure red cell aplasia was significantly higher in cases with the major and bidirectional ABO incompatibility (P < 0.001) with odds ratio (OR): 19.8 [95 % confidence interval (CI): 2.3–2578.9; P < 0.001), and anti-A isohemagglutinin against donor red blood cells (RBCs) in the recipient serum is an important risk factor for this complication. Our results do not show any significant relationship between ABO incompatibility/compatibility on engraftment time and graft failure. The ABO incompatibility increased RBC transfusion burden but did not affect platelet consumption, the incidence and severity of acute and chronic GVHD, patient survivals and non-relapse mortality.
Conclusion
Our findings suggest that allo-HSCT with bidirectional ABO incompatibility with anti-A isohemagglutinins are associated with the occurrence of pure erythroid aplasia. However, ABO incompatibility did not affect the risk for acute and chronic GVHD, survival of patients, and all-HSCT engraftment status.
{"title":"The impact of ABO compatibility/incompatibility between donor and recipient of allogeneic bone marrow transplant on transplant outcomes","authors":"Ehsan Yazdandoust , Abbas Hajifathali , Amir Teimourpour , Sedigheh Amini-Kafiabad , Elham Roshandel","doi":"10.1016/j.trim.2025.102231","DOIUrl":"10.1016/j.trim.2025.102231","url":null,"abstract":"<div><h3>Background</h3><div>ABO blood group mismatch between donor and recipients is not considered as a major contraindication to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, there is still conflicting reports on the impact of ABO incompatibility on allo-HSCT outcomes, including the risk of graft-versus-host disease (GVHD), relapse of underlying disease, and patient survivals.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study in 157 patients who underwent HSCT from October 1st 2019, to September 30th 2023, to determine the effect of ABO compatibility on allo-HSCT outcomes, as evaluating for pure red cell aplasia, engraftment time/status, chronic/acute allo-GVHD, and non-relapse mortality.</div></div><div><h3>Results</h3><div>Overall, 50.3 % of HSCT patients were ABO incompatible and 49.7 % of allo-HSCT patients were ABO compatible. Our findings suggest that the risk of pure red cell aplasia was significantly higher in cases with the major and bidirectional ABO incompatibility (<em>P</em> < 0.001) with odds ratio (OR): 19.8 [95 % confidence interval (CI): 2.3–2578.9; P < 0.001), and anti-A isohemagglutinin against donor red blood cells (RBCs) in the recipient serum is an important risk factor for this complication. Our results do not show any significant relationship between ABO incompatibility/compatibility on engraftment time and graft failure. The ABO incompatibility increased RBC transfusion burden but did not affect platelet consumption, the incidence and severity of acute and chronic GVHD, patient survivals and non-relapse mortality.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that allo-HSCT with bidirectional ABO incompatibility with anti-A isohemagglutinins are associated with the occurrence of pure erythroid aplasia. However, ABO incompatibility did not affect the risk for acute and chronic GVHD, survival of patients, and all-HSCT engraftment status.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102231"},"PeriodicalIF":1.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927462","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 : 2025-05-08DOI: 10.1016/j.trim.2025.102240
Marzieh Izadifard , Mohammad Ahmadvand , Bahram Chahardouli , Mohammad Vaezi , Ghasem Janbabai , Ghazal Seghatoleslami , Mehran Bahrami , Marjan Yaghmaie , Maryam Barkhordar
Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a viable treatment option for acute myeloid leukemia (AML), though it carries risks including delayed immune reconstitution and hematopoietic reconstitution failure. This study aimed to explore the potential of circulating miRNA levels as biomarkers for post-transplant immune reconstitution.
Methods
This observational study was carried out on de novo non-M3 AML patients receiving allo-HSCT from HLA-matched sibling donors at Shariati Hospital, Iran in 2020–2023. Accordingly, the immunophenotype of NK cells, T cells, and B cells was determined by ten-color multiparameter flow cytometry on blood samples collected pre-transplantation and at day +30 post-transplantation. Concurrently, plasma levels of miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p were quantified using quantitative reverse transcription–polymerase chain reaction (RT qPCR).
Results
The expression of miR-638, miR-3613-5p, miR-455-3p, and miR-548a-3p positively correlated with CD4+ T cells, CD4+/CD8+ T cell ratio, CD3−/16+/56− cells, and platelet count. Elevated miR-455-3p and miR-3613-5p expressions were associated with higher CD3−/16+/56− cells (P = 0.0475 and P = 0.0325, respectively). Similarly, miR-638 upregulation correlated with increases in CD4+ T cells (P = 0.0112) and the CD4+/CD8+ T cell ratio (P = 0.006), while miR-548a-3p upregulation was associated with increases in the CD4+/CD8+ T cell ratio (P = 0.0353) and platelet count (P = 0.0191). Conversely, miR-3613-5p and miR-6511b-5p had considerable negative correlations with CD8+ T cells (P = 0.03 and P = 0.0246, respectively), whereas miR-5787 negatively correlated with CD3+/16−/56+ cells (P = 0.025).
Conclusion
Our findings suggest that differentiation of cell subpopulations is regulated by specific miRNAs. Furthermore, miRNA-based strategies may be developed for immunotherapeutic treatments of AML.
{"title":"Plasma-circulating miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p as noninvasive biomarkers of immune reconstitution post-allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients","authors":"Marzieh Izadifard , Mohammad Ahmadvand , Bahram Chahardouli , Mohammad Vaezi , Ghasem Janbabai , Ghazal Seghatoleslami , Mehran Bahrami , Marjan Yaghmaie , Maryam Barkhordar","doi":"10.1016/j.trim.2025.102240","DOIUrl":"10.1016/j.trim.2025.102240","url":null,"abstract":"<div><h3>Introduction</h3><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a viable treatment option for acute myeloid leukemia (AML), though it carries risks including delayed immune reconstitution and hematopoietic reconstitution failure. This study aimed to explore the potential of circulating miRNA levels as biomarkers for post-transplant immune reconstitution.</div></div><div><h3>Methods</h3><div>This observational study was carried out on de novo non-M3 AML patients receiving allo-HSCT from HLA-matched sibling donors at Shariati Hospital, Iran in 2020–2023. Accordingly, the immunophenotype of NK cells, T cells, and B cells was determined by ten-color multiparameter flow cytometry on blood samples collected pre-transplantation and at day +30 post-transplantation. Concurrently, plasma levels of miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p were quantified using quantitative reverse transcription–polymerase chain reaction (RT qPCR).</div></div><div><h3>Results</h3><div>The expression of miR-638, miR-3613-5p, miR-455-3p, and miR-548a-3p positively correlated with CD4<sup>+</sup> T cells, CD4<sup>+</sup>/CD8<sup>+</sup> T cell ratio, CD3<sup>−</sup>/16<sup>+</sup>/56<sup>−</sup> cells, and platelet count. Elevated miR-455-3p and miR-3613-5p expressions were associated with higher CD3<sup>−</sup>/16<sup>+</sup>/56<sup>−</sup> cells (<em>P</em> = 0.0475 and <em>P</em> = 0.0325, respectively). Similarly, miR-638 upregulation correlated with increases in CD4<sup>+</sup> T cells (<em>P</em> = 0.0112) and the CD4<sup>+</sup>/CD8<sup>+</sup> T cell ratio (<em>P</em> = 0.006), while miR-548a-3p upregulation was associated with increases in the CD4<sup>+</sup>/CD8<sup>+</sup> T cell ratio (<em>P</em> = 0.0353) and platelet count (<em>P</em> = 0.0191). Conversely, miR-3613-5p and miR-6511b-5p had considerable negative correlations with CD8<sup>+</sup> T cells (P = 0.03 and <em>P</em> = 0.0246, respectively), whereas miR-5787 negatively correlated with CD3<sup>+</sup>/16<sup>−</sup>/56<sup>+</sup> cells (<em>P</em> = 0.025).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that differentiation of cell subpopulations is regulated by specific miRNAs. Furthermore, miRNA-based strategies may be developed for immunotherapeutic treatments of AML.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102240"},"PeriodicalIF":1.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033467","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 : 2025-05-01DOI: 10.1016/j.trim.2025.102223
Tarun Kumar Suvvari
{"title":"Predictive modeling for organ transplant rejection: The promising role of artificial intelligence and machine learning","authors":"Tarun Kumar Suvvari","doi":"10.1016/j.trim.2025.102223","DOIUrl":"10.1016/j.trim.2025.102223","url":null,"abstract":"","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102223"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711418","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}
Kidney transplantation is the best treatment for patients with End-stage renal disease (ESRD), offering significant improvements in their survival and quality of life. However, immune-mediated rejection of the graft remains a critical challenge. Anti-Human Leukocyte Antigen (HLA) antibodies are well-recognized mediators of acute and chronic rejection. In contrast, the role of non-HLA antibodies particularly donor-specific Anti-MHC class I-related chain A (MICA) antibodies (dsMICA Abs) requires further investigation.
We report the first documented case in India of acute antibody-mediated rejection (AMR) in renal transplant recipients attributed to dsMICA. The patient, an 18-year-old male, developed graft dysfunction post-transplant despite a negative HLA Complement dependent Cytotoxicity crossmatch (CDCXM) and Lysate based Luminex Crossmatch (LumXm) results performed prior to transplantation. A more detailed diagnostic workup revealed the presence of dsMICA Abs, implicating them in the observed AMR. After a targeted treatment regimen of plasmapheresis and intravenous immunoglobulin (IVIG) therapy, the patient showed substantial clinical improvement, marked by declining creatinine levels and then restoration of renal function. This study underscores the clinical significance of dsMICA antibodies in AMR and advocates for the need for routine non-HLA antibody screening in addition to anti-HLA screening post-transplant immunological monitoring.
{"title":"“Virtual crossmatch reveals donor-specific MICA antibodies in antibody mediated rejection: First established Indian case”","authors":"Machiraju Sai Ravi Shankar , Mamidi Neeraja , Mohit Chowdhry , Ayushi Yadav , Sriya Machiraju , Meenakshi Singh , Swarnalata Gowrishanker","doi":"10.1016/j.trim.2025.102229","DOIUrl":"10.1016/j.trim.2025.102229","url":null,"abstract":"<div><div>Kidney transplantation is the best treatment for patients with End-stage renal disease (ESRD), offering significant improvements in their survival and quality of life. However, immune-mediated rejection of the graft remains a critical challenge. Anti-Human Leukocyte Antigen (HLA) antibodies are well-recognized mediators of acute and chronic rejection. In contrast, the role of non-HLA antibodies particularly donor-specific Anti-MHC class I-related chain A (MICA) antibodies (dsMICA Abs) requires further investigation.</div><div>We report the first documented case in India of acute antibody-mediated rejection (AMR) in renal transplant recipients attributed to dsMICA. The patient, an 18-year-old male, developed graft dysfunction post-transplant despite a negative HLA Complement dependent Cytotoxicity crossmatch (CDCXM) and Lysate based Luminex Crossmatch (LumXm) results performed prior to transplantation. A more detailed diagnostic workup revealed the presence of dsMICA Abs, implicating them in the observed AMR. After a targeted treatment regimen of plasmapheresis and intravenous immunoglobulin (IVIG) therapy, the patient showed substantial clinical improvement, marked by declining creatinine levels and then restoration of renal function. This study underscores the clinical significance of dsMICA antibodies in AMR and advocates for the need for routine non-HLA antibody screening in addition to anti-HLA screening post-transplant immunological monitoring.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102229"},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874286","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 : 2025-04-22DOI: 10.1016/j.trim.2025.102232
Meera Patel , Supriya Singh , Puneet Dhillon , Sofia Molina Garcia , Michael Sheu , Sonya Kothadia , Ali Mushtaq , Aneela Majeed
Background
Concurrent cytomegalovirus infection (CMVi) and gastrointestinal graft-versus-host disease (GI-GVHD) poses significant risks for increased morbidity and mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Primary prophylaxis with letermovir therapy has been shown to decrease the risk of CMV reactivation, but studies examining this relationship after GI-GVHD are lacking. We reviewed our center's outcomes associated with concomitant CMVi and GI-GVHD before and after our adopting the use of letermovir therapy for CMV prophylaxis in 2017.
Methods
This was a single-center, retrospective study of allo-HCT patients who developed GI-GVHD and CMVi between June 2013 and June 2021. CMVi was defined as detection of CMV in the blood or detection of CMV in sampled tissue. CMV colitis was defined as biopsy-proven tissue-invasive CMV disease. The primary outcome was one year survival.
Results
We evaluated 43 allo-HCT patients who had concomitant CMVi and GI-GVHD. Out of 43 patients, 40 of them (93 %) had a high risk serostatus for CMVi (recipient seropositive). CMV colitis was confirmed by biopsy in 18 patients (42 %) and was clinically suspected in 20 patients (47 %). Twenty-five patients (58 %) developed CMV viremia, and 18 of them developed concomitant biopsy proven CMV colitis. Nine patients (21 %) received letermovir therapy for primary CMV prophylaxis, and 7 of these 9 patients (78 %) developed breakthrough CMVi while receiving prophylaxis. The median time from HCT to CMVi was similar between the group that received letermovir prophylaxis and the group that did not. Median peak CMV levels were lower in the prophylaxis group. Overall survival rates at one and five years were 65 % and 21 %, respectively, with the mortality reaching 25 % at 164 days and 50 % at 480 days. There was no statistically significant difference in one year survival between patients with CMV viremia but without colitis compared to those with CMV viremia and colitis (p = 0.648, 95 % CI 0.3–1.57). One-year survival was also not statistically different between patients who received letermovir prophylaxis compared to those who did not (p = 0.250, 95 % CI 0.60–6.97) or between patients with high grade GI-GVHD (grade 3–4) and low-grade GI-GVHD (grade 1–2; p = 0.277, 95 % CI 0.64–4.83).
Conclusion
In this high-risk cohort with GI-GVHD and CMVi, the peak viral load was lower in the group that received letermovir prophylaxis, but the median time to onset of CMVi and survival were not statistically different. The majority of patients in the letermovir prophylaxis group developed CMVi while on letermovir. Further investigations with larger sample sizes may better assess the impact of letermovir therapy on patient survival and the development of CMVi outcomes in the setting of GI-GVHD in the era of pre-emptive prophyl
背景巨细胞病毒感染（CMVi）和胃肠道移植物抗宿主病（GI-GVHD）并发对接受同种异体造血细胞移植（alloo - hct）的患者的发病率和死亡率增加具有显著的风险。莱替莫韦治疗的初级预防已被证明可以降低巨细胞病毒再激活的风险，但缺乏对GI-GVHD后这种关系的研究。我们回顾了本中心在2017年采用莱替莫韦治疗CMV预防前后与CMVi和GI-GVHD相关的结果。方法：这是一项单中心、回顾性研究，研究对象是2013年6月至2021年6月期间发生GI-GVHD和CMVi的同种异体hct患者。CMVi定义为血液中CMV的检测或样本组织中CMV的检测。巨细胞病毒结肠炎被定义为活检证实的组织侵袭性巨细胞病毒疾病。主要终点为1年生存率。结果我们评估了43例伴有CMVi和GI-GVHD的allo-HCT患者。在43例患者中，其中40例（93%）具有CMVi高危血清状态（受体血清阳性）。18例（42%）患者活检证实巨细胞病毒结肠炎，20例（47%）患者临床怀疑巨细胞病毒结肠炎。25例（58%）患者发生巨细胞病毒血症，其中18例并发活检证实巨细胞病毒结肠炎。9名患者（21%）接受莱特莫韦治疗进行原发性巨细胞病毒预防，其中7名患者（78%）在接受预防治疗时出现突破性巨细胞病毒。从HCT到CMVi的中位时间在接受雷特莫韦预防组和未接受雷特莫韦预防组之间相似。预防组CMV的中位峰值水平较低。1年和5年的总生存率分别为65%和21%，164天和480天的死亡率分别为25%和50%。巨细胞病毒血症合并结肠炎患者与巨细胞病毒血症合并结肠炎患者的1年生存率差异无统计学意义（p = 0.648, 95% CI 0.3-1.57）。接受雷替莫韦预防的患者与未接受雷替莫预防的患者的一年生存率也无统计学差异（p = 0.250, 95% CI 0.60-6.97），高级别GI-GVHD患者（3-4级）与低级别GI-GVHD患者(1-2级；p = 0.277, 95% CI 0.64-4.83)。结论在伴有GI-GVHD和CMVi的高危队列中，接受莱替韦预防组的病毒峰值载量较低，但CMVi发病的中位时间和生存期无统计学差异。雷替莫韦预防组的大多数患者在使用雷替莫韦时发生了CMVi。在预防性抗病毒治疗时代，更大样本量的进一步研究可能更好地评估莱替莫韦治疗对GI-GVHD患者生存和CMVi结局发展的影响。
{"title":"Outcomes of CMV infection in the setting of gastrointestinal graft-vs.-host disease in the era of pre-emptive and prophylactic antiviral therapy","authors":"Meera Patel , Supriya Singh , Puneet Dhillon , Sofia Molina Garcia , Michael Sheu , Sonya Kothadia , Ali Mushtaq , Aneela Majeed","doi":"10.1016/j.trim.2025.102232","DOIUrl":"10.1016/j.trim.2025.102232","url":null,"abstract":"<div><h3>Background</h3><div>Concurrent cytomegalovirus infection (CMVi) and gastrointestinal graft-versus-host disease (GI-GVHD) poses significant risks for increased morbidity and mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Primary prophylaxis with letermovir therapy has been shown to decrease the risk of CMV reactivation, but studies examining this relationship after GI-GVHD are lacking. We reviewed our center's outcomes associated with concomitant CMVi and GI-GVHD before and after our adopting the use of letermovir therapy for CMV prophylaxis in 2017.</div></div><div><h3>Methods</h3><div>This was a single-center, retrospective study of allo-HCT patients who developed GI-GVHD and CMVi between June 2013 and June 2021. CMVi was defined as detection of CMV in the blood or detection of CMV in sampled tissue. CMV colitis was defined as biopsy-proven tissue-invasive CMV disease. The primary outcome was one year survival.</div></div><div><h3>Results</h3><div>We evaluated 43 allo-HCT patients who had concomitant CMVi and GI-GVHD. Out of 43 patients, 40 of them (93 %) had a high risk serostatus for CMVi (recipient seropositive). CMV colitis was confirmed by biopsy in 18 patients (42 %) and was clinically suspected in 20 patients (47 %). Twenty-five patients (58 %) developed CMV viremia, and 18 of them developed concomitant biopsy proven CMV colitis. Nine patients (21 %) received letermovir therapy for primary CMV prophylaxis, and 7 of these 9 patients (78 %) developed breakthrough CMVi while receiving prophylaxis. The median time from HCT to CMVi was similar between the group that received letermovir prophylaxis and the group that did not. Median peak CMV levels were lower in the prophylaxis group. Overall survival rates at one and five years were 65 % and 21 %, respectively, with the mortality reaching 25 % at 164 days and 50 % at 480 days. There was no statistically significant difference in one year survival between patients with CMV viremia but without colitis compared to those with CMV viremia and colitis (<em>p</em> = 0.648, 95 % CI 0.3–1.57). One-year survival was also not statistically different between patients who received letermovir prophylaxis compared to those who did not (<em>p</em> = 0.250, 95 % CI 0.60–6.97) or between patients with high grade GI-GVHD (grade 3–4) and low-grade GI-GVHD (grade 1–2; <em>p</em> = 0.277, 95 % CI 0.64–4.83).</div></div><div><h3>Conclusion</h3><div>In this high-risk cohort with GI-GVHD and CMVi, the peak viral load was lower in the group that received letermovir prophylaxis, but the median time to onset of CMVi and survival were not statistically different. The majority of patients in the letermovir prophylaxis group developed CMVi while on letermovir. Further investigations with larger sample sizes may better assess the impact of letermovir therapy on patient survival and the development of CMVi outcomes in the setting of GI-GVHD in the era of pre-emptive prophyl","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102232"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874285","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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