Transplant immunology最新文献

{"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":"2025-09-01","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":"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":"2025-09-01","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":"Syngeneic hematopoietic stem cell transplantation from an identical twin sister in an AML patient: “A case report highlighting accelerated engraftment and reduced transfusion requirements”","authors":"Ehsan Yazdandoust ,&nbsp;Abbas Hajifathali ,&nbsp;Zeinab Kaboli ,&nbsp;Sedigheh Amini-Kafiabad","doi":"10.1016/j.trim.2025.102267","DOIUrl":"10.1016/j.trim.2025.102267","url":null,"abstract":"<div><h3>Background and objective</h3><div>Hematopoietic stem cell transplantation (HSCT) is among the most effective immunotherapeutic strategies for treating hematologic malignancies in both pediatric and adult patients. Its global use has been steadily increasing. Patients undergoing HSCT commonly require transfusion support with blood products until engraftment is achieved, and transfusion requirements can significantly affect post-transplant outcomes. Despite advancements that have improved survival rates, transplant-related mortality (TRM) continues to be a major obstacle to optimal outcomes.</div></div><div><h3>Case presentation</h3><div>We present the case of a 46-year-old woman diagnosed with acute myeloid leukemia (AML) harboring an FLT3-ITD mutation, who underwent allogeneic HSCT. The donor was her identical twin sister, with full HLA compatibility (a 10/10 match) and an identical ABO blood group (O positive). Notably, the patient exhibited rapid neutrophil and platelet engraftment by day +9, which is earlier than typically observed in transplants from fully matched related or unrelated donors. Furthermore, the patient did not require any red blood cell or platelet transfusions during the transplantation period and developed no signs of acute or chronic graft-versus-host disease (GVHD). She has remained disease-free with no evidence of relapse for over three years post-transplant.</div></div><div><h3>Conclusion</h3><div>HSCT from an identical twin donor may provide favorable clinical outcomes, including accelerated engraftment and reduced transfusion needs during the transplantation process.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102267"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656988","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":"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":"2025-09-01","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":"Early post-lung transplant cell-free DNA levels are associated with baseline lung allograft function","authors":"Andrea Zajacova ,&nbsp;Majd Alkhouri ,&nbsp;Goncalo Ferrao ,&nbsp;Miray Guney ,&nbsp;David Rezac ,&nbsp;Kristyna Vyskocilova ,&nbsp;Tereza Kotowski ,&nbsp;Alzbeta Dutkova ,&nbsp;Eliska Dvorackova ,&nbsp;Robert Lischke ,&nbsp;Libor Fila ,&nbsp;David J. Ross ,&nbsp;Bart Vanaudenaerde ,&nbsp;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":"2025-09-01","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}

{"title":"Successful use of belumosudil in a patient with chronic ocular GVHD: A case report","authors":"Xiaoli Lv ,&nbsp;Huibo Li ,&nbsp;Zhijian Li ,&nbsp;Di Jin ,&nbsp;Fei Leng ,&nbsp;Jie Liu ,&nbsp;Dan Guo ,&nbsp;Shengjin Fan ,&nbsp;Sheng Su","doi":"10.1016/j.trim.2025.102271","DOIUrl":"10.1016/j.trim.2025.102271","url":null,"abstract":"<div><h3>Background</h3><div>Belumosudil is a selective ROCK2 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients who have failed at least two prior systemic therapies. By inhibiting ROCK2, Belumosudil can down-regulate the secretion of IL-21 and IL-17, and up-regulate regulatory T cells (Tregs), which serve to attenuate the inflammatory response. In addition, it can act as an antifibrotic by inhibiting the Rho-ROCK-MRTF pathway, as well as down-regulating the expression of pro-fibrotic genes and TGF-β signaling. Selective inhibition of ROCK2 also reduces M2-like macrophages and choroidal neovascularization, which further exerts antifibrotic effects. Therefore, belumosudil shows great potential in the treatment of chronic Graft-Versus-Host-Disease (cGVHD).</div></div><div><h3>Case presentation</h3><div>We report the clinical course of a 39-year-old man with severe progressive chronic ocular GVHD (oGVHD), who showed significant improvement in ocular surface damage, including damage to the cornea and meibomian glands, as well as dry eye symptoms, after oral administration of belumosudil. Corneal leukoplakia and neovascularization were significantly reduced after treatment. Moreover, the patient's ocular surface symptoms remained stable without deterioration after cataract surgery. The patient's quality of life was significantly enhanced.</div></div><div><h3>Conclusion</h3><div>We report the clinical outcomes of a patient with chronic oGVHD treated with belumosudil. The patient's clinical symptoms significantly improved, especially inflammation of the meibomian gland, corneal leukoplakia, and neovascularization. This highlights its application value in patients with cGVHD and provides a promising treatment option for patients with oGVHD.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102271"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"2025-09-01","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":"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 ,&nbsp;Jia-yan Leng ,&nbsp;Chen-yun Xu ,&nbsp;Chao-ran Lv ,&nbsp;Zhen Qian ,&nbsp;Yan Zhou ,&nbsp;Di Yu ,&nbsp;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/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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102241"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","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}

{"title":"Rapamycin-modified CD169low/-tolDC promotes skin graft survival in mice via IL-10+Breg","authors":"Xi Lu ,&nbsp;Yu-di Han ,&nbsp;Xiao-ran Zu ,&nbsp;Jin-can Huang ,&nbsp;Li Li ,&nbsp;Meng Wang ,&nbsp;Yu-Ting Wang ,&nbsp;Ling-li Guo ,&nbsp;Lin Zhou ,&nbsp;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":"2025-06-01","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}

{"title":"The impact of ABO compatibility/incompatibility between donor and recipient of allogeneic bone marrow transplant on transplant outcomes","authors":"Ehsan Yazdandoust ,&nbsp;Abbas Hajifathali ,&nbsp;Amir Teimourpour ,&nbsp;Sedigheh Amini-Kafiabad ,&nbsp;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> &lt; 0.001) with odds ratio (OR): 19.8 [95 % confidence interval (CI): 2.3–2578.9; P &lt; 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":"2025-06-01","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}