Transplant immunology最新文献

{"title":"Testing controls demonstrates a high prevalence of non-HLA antibody positivity using pre-defined cutoff threshold in a bead-based assay using healthy control population","authors":"A. Agrawal ,&nbsp;M. Zuccarelli ,&nbsp;L.L. Wakefield ,&nbsp;C.A. Schinstock ,&nbsp;M.J. Gandhi ,&nbsp;A.J. Bentall","doi":"10.1016/j.trim.2025.102265","DOIUrl":"10.1016/j.trim.2025.102265","url":null,"abstract":"<div><h3>Background</h3><div>Measuring non-HLA antibodies is a potentially important tool in assessing allograft dysfunction and needs to be correlated with clinical outcomes. Thus, determining the antibody distribution in healthy populations is important before correlating with clinical events. Using male blood donors, we selected a low immunological risk control cohort.</div></div><div><h3>Methods</h3><div>We analyzed samples from 92 male, non-transfused blood donors (donors) to assess the detection of antibodies in a normal population cohort using a non-HLA 33 antigen multiplex commercial assay.</div></div><div><h3>Results</h3><div>At manufacturer's suggested cutoff threshold (COT) of 75 % percentile, no donors had negative results and at 95 % percentile only three donors were negative across all 33 antigens. At each of the manufacturer's COT, the median (IQR) number positive antibody bead tests per donor was 13 (10–17), 11 (8–13) and 7 (5–10) at 75th, 85th and 95th percentile COT, respectively. There was poor correlation between manufacturer's COT and locally generated COT (range <em>r</em> = 0.520 to 0.595). The percentage of donors who had three or more positive antibody bead tests was: 98.9 % at 75th COT; 95.7 % at 85th COT and 93.5 % at 95th COT.</div></div><div><h3>Conclusions</h3><div>Considering the high proportion of positive results in a low immunological risk cohort, application of non-HLA antibody measurement in a diseased cohort is not optimal, and difficult to correlate with clinical events. Further studies to determine normal detection rates are needed for assay COT and clinical application in diseases.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102265"},"PeriodicalIF":1.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665922","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}

{"title":"Dynamics of monocytic myeloid-derived suppressor cell recovery and interleukin-10 production on graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation","authors":"Arsa Thammahong ,&nbsp;Kitsada Wudhikarn ,&nbsp;Ponlapat Rojnuckarin ,&nbsp;Patsita Kansuwan ,&nbsp;Udomsak Bunworasate ,&nbsp;Chantiya Chanswangphuwana","doi":"10.1016/j.trim.2025.102263","DOIUrl":"10.1016/j.trim.2025.102263","url":null,"abstract":"<div><h3>Background</h3><div>Myeloid-derived suppressor cells (MDSCs) suppress immune responses. We hypothesized that MDSCs and their related cytokines/chemokines after receiving allogeneic hematopoietic cell transplantation (allo-HCT) impact graft-versus-host disease (GVHD) and infectious complications.</div></div><div><h3>Methods</h3><div>This study investigated the dynamics of MDSCs recovery using flow cytometry. Cytokines/chemokines were measured by the Luminex assay and correlated with clinical outcomes.</div></div><div><h3>Results</h3><div>Forty-nine patients who underwent allo-HCT at King Chulalongkorn Memorial Hospital from 2022 to 2023 were enrolled. The median age was 42 years. Most cases (81.6 %) were acute leukemia. Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (85.7 %) or haploidentical donors (14.3 %). Forty-six patients (93.9 %) received myeloablative conditioning regimens. GVHD prophylaxis regimens were calcineurin inhibitor plus methotrexate (67.3 %) and post-transplantation cyclophosphamide (32.7 %). Acute GVHD occurred in 9 (18.4 %) patients with a median onset of 35 days. The percentage of monocytic MDSC (M-MDSC), interleukin-10 (IL-10) and CXCL2 levels on day+28 of acute GVHD patients were all significantly lower than non-GVHD patients (0.26 % vs. 0.55 %, <em>p</em> = 0.048, 15.45 pg/ml vs. 23.53 pg/ml, <em>p</em> = 0.041, and 201.44 pg/ml vs. 428.42 pg/ml, <em>p</em> = 0.029, respectively). Cytomegalovirus (CMV) reactivation was detected in 69.4 % of patients with a median onset of 39 days. CMV reactivation was related to higher M-MDSC percentage on day+14 and IL-10 on day+28 compared with no reactivation (0.76 % vs. 0.22 %, <em>p</em> = 0.047 and 24.35 pg/ml vs. 16.42 pg/ml, <em>p</em> = 0.003, respectively).</div></div><div><h3>Conclusion</h3><div>Delayed M-MDSC reconstitution and low IL-10 were associated with acute GVHD, while high numbers of M-MDSCs and higher IL-10 levels increased the risk of CMV reactivation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102263"},"PeriodicalIF":1.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490885","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}

{"title":"Donor lymphocyte infusion-based therapy for relapsed adult T-cell leukemia/lymphoma after HLA-haploidentical hematopoietic stem cell transplantation","authors":"Shinichi Katsuoka ,&nbsp;Hidehiro Itonaga ,&nbsp;Miki Hashimoto ,&nbsp;Hikaru Sakamoto ,&nbsp;Takafumi Furumoto ,&nbsp;Yuichi Yamada ,&nbsp;Takeharu Kato ,&nbsp;Makiko Horai ,&nbsp;Shinya Sato ,&nbsp;Koji Ando ,&nbsp;Kazuhiro Nagai ,&nbsp;Nariyoshi Matsumoto ,&nbsp;Daisuke Sasaki ,&nbsp;Hiroo Hasegawa ,&nbsp;Yoshitaka Imaizumi ,&nbsp;Katsunori Yanagihara ,&nbsp;Yasushi Miyazaki","doi":"10.1016/j.trim.2025.102262","DOIUrl":"10.1016/j.trim.2025.102262","url":null,"abstract":"<div><div>Donor lymphocyte infusion (DLI) combined with chemotherapy is an effective therapy for relapsed adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-matched related donor or matched unrelated donor. The 1-year incidence of ATL relapse is 28 % after HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide. However, the efficacy of DLI for relapsed ATL after haplo-HSCT remains unclear. Here, we present the case of a 61-year-old woman diagnosed with ATL who underwent haplo-HSCT from an HLA-haploidentical relative donor. On day +164 after transplantation, the patient experienced ATL relapse. Tacrolimus was tapered and discontinued on day +216; however, ATL progressed. Since the patient did not develop graft-versus-host disease (GVHD) after the discontinuation of tacrolimus, DLI following chemotherapy was performed for relapsed ATL. The patient achieved complete remission without severe GVHD after the 6th DLI treatment. This remission has been sustained for over 15 months with 13 DLI treatments. These results suggest the potential of DLI combined with chemotherapy as a treatment option for patients with relapsed ATL after haplo-HSCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102262"},"PeriodicalIF":1.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366002","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}

{"title":"Efficacy of waitlist desensitization for lung candidates is limited by antibody rebound","authors":"David Pinelli ,&nbsp;Jennifer Wright ,&nbsp;Amanda Kamar ,&nbsp;Ambalavanan Arunachalam ,&nbsp;Mrinalini Venkata Subramani ,&nbsp;Chitaru Kurihara ,&nbsp;Ankit Bharat ,&nbsp;Catherine Myers","doi":"10.1016/j.trim.2025.102261","DOIUrl":"10.1016/j.trim.2025.102261","url":null,"abstract":"<div><div>HLA antibodies remain a barrier to lung transplantation due to the risk of antibody-mediated rejection (AMR). Desensitization is an option to lower antibody levels and increase access to transplant by reducing risk of AMR. However, concerns remain regarding the efficacy, durability, and risks of administering this treatment while waiting for deceased donor offers. We performed longitudinal antibody assessments for 15 highly sensitized lung candidates undergoing desensitization with plasmapheresis-based treatment protocols. Of the 14 patients transplanted, a significant decrease in overall antibody level was observed in the 2 of 4 patients transplanted within 15 days of the end of their first treatment. Conversely, of the 10 who were transplanted more than 15 days after first treatment, 7 patients rebounded to pre-treatment levels or higher within 3–4 weeks. For the 3 patients in this group who showed a durable decrease, this effect did not manifest until months following treatment. When comparing outcomes for the desensitization cohort against a control group that received treatment post-transplant, no significant differences in survival or acute rejection were observed. These results demonstrate that while plasmapheresis-based waitlist desensitization can effectively remove or reduce the level of HLA antibodies, rebound limits its effectiveness for most patients. To promote successful outcomes, pre-transplant therapy should be targeted to candidates with high lung composite allocation scores likely to be transplanted within the first week after treatment, while aggressive post-transplant immunosuppression may be a safer approach for most highly sensitized patients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102261"},"PeriodicalIF":1.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295014","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}

{"title":"Identification of genes associated with liver ischemia-reperfusion injury after liver transplantation by WGCNA and PPI network analyses","authors":"Li Jin ,&nbsp;Zhuo Cheng ,&nbsp;Bo Yuan ,&nbsp;Siming Qu ,&nbsp;Jie Lin ,&nbsp;Lin Deng ,&nbsp;Benkai Wei ,&nbsp;Hangpin Wang ,&nbsp;Youzhi Ye ,&nbsp;Zhong Zeng ,&nbsp;Hanfei Huang","doi":"10.1016/j.trim.2025.102249","DOIUrl":"10.1016/j.trim.2025.102249","url":null,"abstract":"<div><div>Liver transplantation is the only effective treatment for end-stage liver disease. The success of transplantation largely relies on liver ischemia/reperfusion injury (LIRI). However, the pathogenesis of LIRI remains unclear. In this study, we used the public dataset GSE12720, which contains liver transplants from both living and deceased donors, to identify differentially expressed genes (DEGs) before and after reperfusion. Weighted gene co-expression network analysis (WGCNA) was used to identify related genes. A protein–protein interaction network containing 85 overlapping DEGs and WGCNA genes was constructed. Using Molecular Complex Detection and cytoHubba plug-ins in Cytoscape and Kyoto Encyclopedia of Genes and Genomes analyses, we identified 5 core pathways and 13 hub genes (<em>IL-1β, JUN, TNFAIP3, CCL2, ICAM1, CCL20, SOCS3, IRF1, BIRC3, GADD45B, MYC, CCL4, and BCL2A1</em>). These findings were validated using two independent datasets (GSE14951 and GSE15480) and a mouse LIRI model, which effectively confirmed the expression levels of 13 hub genes. This study aimed to use advanced bioinformatics methods to investigate hub genes related to LIRI to identify new biomarkers and improve our understanding of LIRI pathogenesis.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102249"},"PeriodicalIF":1.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286589","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}

{"title":"Comparative efficacy of Naringenin and Sinomenine in facilitating the differentiation of mouse hematopoietic stem cells into immature dendritic cells to promote transplantation immunological regulation","authors":"Cuixiang Xu ,&nbsp;Xiangrong Zhao ,&nbsp;Zejiaxin Niu ,&nbsp;Ying Wang ,&nbsp;Xinlu Jiang ,&nbsp;Jiaxin Tian ,&nbsp;Yangmeng Feng ,&nbsp;Xiaoyan Huang ,&nbsp;Puxun Tian","doi":"10.1016/j.trim.2025.102260","DOIUrl":"10.1016/j.trim.2025.102260","url":null,"abstract":"<div><h3>Objective</h3><div>Immature dendritic cells (imDC) are crucial in facilitating transplant immunological regulation. However, imDC is readily amenable to maturation. Sinomenine (Sin) naringin (Nar) are traditional Chinese medicine with immunoregulation and anti-inflammatory activities. We investigated the effect of Sin and Nar on the generation of immature dendritic cells (imDC) and their ability to prolong the survival of skin allografts in mice.</div></div><div><h3>Methods</h3><div>Hematopoietic stem cells (HSC) obtained from bone marrow prompted to develop into immature dendritic cells (imDC) through treatment with Sin (Sin-HSC-imDC) or Nar (Nar-HSC-imDC). The cell counting kit-8 (CCK-8) assay was employed to assess the differentiating efficacy of Sin-HSC-imDC and Nar-HSC-imDC. DC surface markers and apoptosis following lipopolysaccharide (LPS) treatment were assessed by flow cytometry, while apoptosis-related genes using qPCR. The impact of Sin-HSC-imDC and Nar-HSC-imDC on the generation of regulatory T cells (Tregs) was evaluated by mixed lymphocyte reactions. Cytokine expression was quantified using enzyme-linked immunoassays (ELISA). The immunomodulatory effects of Sin-HSC-imDC and Nar-HSC-imDC were evaluated by performing skin transplantation experiments in Balb/c mice recipients models. Kaplan-Meier technique was employed for graft survival outcomes.</div></div><div><h3>Results</h3><div>In vitro assays, in comparison to Sin-HSC-imDC, Nar-HSC-imDC had higher CD11c expression and lower CD80 as markers for imDCs (<em>P</em> <em>&lt;</em> <em>0.05</em>) and promoted the generation of Tregs proliferation (<em>P</em> <em>&lt;</em> <em>0.05</em>). Interleukin 2 (IL-2) and interferon gamma (IFN-γ) levels diminished in Nar-HSC-imDC groups (<em>P</em> <em>&lt;</em> <em>0.05</em>), but interleukin 10 (IL-10) and transforming growth factor-beta (TGF-β) levels elevated (<em>P</em> <em>&lt;</em> <em>0.05</em>). And the apoptosis rate of Nar-HSC-DC increased significantly after LPS treatment (<em>P</em> <em>&lt;</em> <em>0.05</em>). In vivo assays, when Balb/c mice received Nar-HSC-imDC or Sin-HSC-imDC via the tail vein seven days before skin transplantation, mice from the Nar-HSC-imDC group had increased CD4⁺CD25⁺CD127⁻ Tregs proliferation in the spleen (<em>P</em> <em>&lt;</em> <em>0.05</em>), which prolonged skin graft survival, and that was better than in Sin-HSC-imDC group.</div></div><div><h3>Conclusion</h3><div>Nar was exposured more efficient in inducing differentiation of HSC into imDC than Sin. Nar-HSC-imDC had stronger ability in inducing specific immune hypo-responsiveness than Sin-HSC-imDC.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102260"},"PeriodicalIF":1.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262741","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}

{"title":"Serum PD-L1 and CTLA-4 levels as biomarkers of acute rejection and renal dysfunction in kidney transplant recipients","authors":"Angelica Canossi ,&nbsp;Fabio Vistoli ,&nbsp;Pierluigi Sebastiani ,&nbsp;Alessia Colanardi ,&nbsp;Tiziana Del Beato ,&nbsp;Alessandra Panarese","doi":"10.1016/j.trim.2025.102250","DOIUrl":"10.1016/j.trim.2025.102250","url":null,"abstract":"<div><h3>Purpose</h3><div>Acute rejection in kidney transplantation is a critical barrier to long-term graft survival and the PD-1/PD-L1 and CTLA-4 molecules are crucial for the tolerance of alloreactive T cells against tubular epithelial cells. Our study aims to assess the role of these soluble PD-L1 and CTLA-4 molecules as biomarkers for <em>non-invasive</em> immunosurveillance after renal transplantation.</div></div><div><h3>Methods</h3><div>Blood samples from 65 recipients were investigated for serum sPD-L1 and sCTLA-4 molecules at the time of kidney transplantation (baseline), in 3 time-points (15, 60 and 365 days) post-transplant, and when acute rejection (ACR) was suspected. Samples and standards were processed in duplicate using sandwich ELISA.</div></div><div><h3>Results</h3><div>We revealed dynamic changes in serum expression over time, with a significant decrease from the time of kidney transplantation to the various monitoring points, except at the time of acute rejection when the levels increased. Multivariable logistic regression revealed that the sPD-L1 15-day post-transplant is an independent variable for ACR onset (AOR = 1.196 <em>p</em> = 0.020), and with a moderate discriminatory power (AUC = 0.717, <em>p</em> = 0.031), together with PD-L1 60 days, for the occurrence of rejection within 1 year from transplant. sPD-L1 after 15 days shows a predictive role also for DGF (AUC = 0.738, <em>p</em> = 0.001) and graft dysfunction at 60 days (AUC = 0.672, <em>p</em> = 0.022). Furthermore, a higher 15-day expression of sCTLA-4 in patients with ACR compared with those with stable graft (114.8 pg/mL vs. 67.8 pg/mL, <em>p</em> = 0.018) was reported.</div></div><div><h3>Conclusion</h3><div>These analyses suggest the potential role of these serum molecules as dynamic biomarkers of inflammation and immunoregulation in AKI and acute rejection; they may indicate new immunotherapy targets, useful for modulating tolerance and assist the clinician in identifying patients at risk of rejection or kidney failure.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102250"},"PeriodicalIF":1.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240887","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}

{"title":"Identification of allogeneic and xenogeneic neural stem cells' immunogenicity in the brain and strategies to alleviate transplantation rejection","authors":"Xiangyu Ma ,&nbsp;Ho Jin Lee ,&nbsp;Dong Oh. Kim ,&nbsp;Young Do Kwon ,&nbsp;Geun-Hyoung Ha ,&nbsp;Chung Kwon Kim ,&nbsp;Hyun Nam ,&nbsp;Je Young Yeon ,&nbsp;Kyunghoon Lee ,&nbsp;Sun-Ho Lee ,&nbsp;Kyeung Min Joo","doi":"10.1016/j.trim.2025.102247","DOIUrl":"10.1016/j.trim.2025.102247","url":null,"abstract":"<div><div>Neural stem cells (NSCs) are a promising therapy for central nervous system (CNS) disorders, yet post-transplant immune rejection critically compromises their survival and efficacy. In this study, we demonstrated the neuroinflammatory responses triggered by syngeneic, allogeneic, and xenogeneic NSCs transplantation, and evaluated the immunosuppressive effects of cyclosporine A (CyA) and methylprednisolone (MP) on graft rejection. Our findings revealed that xenogeneic NSCs transplantation induced infiltration of neutrophils (<em>p</em> &lt; 0.0001<strong>)</strong>, microglia/macrophages (<em>p</em> &lt; 0.0001<strong>)</strong>, CD4⁺ and CD8⁺ T cells (<em>p</em> &lt; 0.0001<strong>)</strong>, while allogeneic transplantation primarily triggered microglia/macrophages (<em>p</em> &lt; 0.0005) recruitment. Both transplantation types caused a sharp decline in grafted cell numbers (<em>p</em> &lt; 0.005). Combinatorial CyA and MP treatment significantly attenuated xenogeneic immune rejection and markedly increased surviving graft cells in the brain. Similarly, MP monotherapy effectively reduced allogeneic rejection and enhanced transplanted cell survival. Overall, allogeneic NSCs transplantation primarily triggers innate immunity, while xenogeneic transplantation causes both innate and adaptive immune responses. Accordingly, xenogeneic transplantation required combined CyA and MP therapy, whereas MP monotherapy mitigated rejection in allogeneic transplantation. Our findings may offer a strategy to mitigate transplantation rejection of allogeneic and xenogeneic NSCs in the brain, thereby optimizing the microenvironment for NSC-based therapies in preclinical and clinical applications for various CNS disorders.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102247"},"PeriodicalIF":1.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222642","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}

{"title":"Immunosuppression minimization and withdrawal in liver transplantation: The “holy grail”?","authors":"V.U. Lakshmi ,&nbsp;Mohammed Riyas ,&nbsp;Dinesh Balakrishnan ,&nbsp;M.P. Narmadha ,&nbsp;S. Sudhindran","doi":"10.1016/j.trim.2025.102248","DOIUrl":"10.1016/j.trim.2025.102248","url":null,"abstract":"<div><div>Liver transplantation typically necessitates the use of life long immunosuppressive drugs, to suppress the immune system and minimize the risk of rejection. Prolonged use of immunosuppressive drugs can, however, lead to various side effects, including an increased risk of infections, renal dysfunction, and several metabolic complications. To address this, transplant professionals work to tailor immunosuppression to the patient needs, with the ultimate goal of minimizing drug doses.The “holy grail” of immunosuppression following liver transplantation has been its complete withdrawal. Over the past decade, researchers have juggled with immunosuppression minimization in recipients of liver grafts, but the results were disparate due to the diversity in study designs and limited sample size. Nevertheless, immunosuppression withdrawal has been observed possible in approximately 20 % of strictly selected recipients, particularly in extremes of age and when performed over a prolonged period. The predominant stumbling-block was the occurrence of rejection during the process of immunosuppression withdrawal. Currently, there is a lack of scientific evidence for selecting patients in whom immunosuppressant minimization would be possible without risk of allograft rejection and on the precise methods of immunosuppression withdrawal.The development of clinical tools for personalized medication adjustments and a broader comprehension of the pathogenesis of late graft rejection are essential for this. This article centers on the physiological mechanisms of immune tolerance, strategies for minimizing and withdrawing immunosuppression after liver transplantation, and the biomarkers indicative of sustained tolerance in liver transplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102248"},"PeriodicalIF":1.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226842","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}

{"title":"Recombinant human thrombopoietin reduces the risk of acute graft-versus-host-disease and its mechanism","authors":"Hairong Fei ,&nbsp;Xiaodan Liu ,&nbsp;Xiaolin Ma ,&nbsp;Feng Hou ,&nbsp;Peng Jiang ,&nbsp;Lingjie Sun ,&nbsp;Shanshan Liu ,&nbsp;Tianlan Li ,&nbsp;Chunting Zhao","doi":"10.1016/j.trim.2025.102246","DOIUrl":"10.1016/j.trim.2025.102246","url":null,"abstract":"<div><h3>Objective</h3><div>Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at <em>P</em> &lt; 0.05. <em>P</em> &gt; 0.05 was considered statistically significant. All experiments were repeated for 3 times.</div></div><div><h3>Results</h3><div>Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (<em>P</em> = 0.007 and <em>P</em> = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation.</div></div><div><h3>Conclusions</h3><div>rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102246"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209629","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}