Transplant immunology最新文献

{"title":"Identification of key predictors of acute GVHD in pediatric acute Leukemia using machine learning methods","authors":"İlknur Buçan Kırkbir ,&nbsp;Hacer Kobya Bulut","doi":"10.1016/j.trim.2025.102318","DOIUrl":"10.1016/j.trim.2025.102318","url":null,"abstract":"<div><h3>Backround</h3><div>Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for leukemia. Allogeneic Hematopoietic cell transplantation (HCT), in which stem cells from a healthy donor are used, carries significant risks, including graft versus host disease (GVHD), a severe complication that leads to high morbidity and mortality. This study aimed to identify significant predictors of acute GVHD (aGVHD) in pediatric patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).</div></div><div><h3>Methods</h3><div>This retrospective study analyzed the predictors of aGVHD in pediatric patients using different machine learning methods: Random Forest (RF), Logistic Regression (LR), and Boruta. The dataset was obtained from the UCI machine learning open-source database, and after balancing the class distribution of the dependent variable aGVHD using the Synthetic Minority Oversampling Technique (SMOTE), a total of 124 pediatric patients, including demographic and clinical variables, were analyzed using the R open-source programming language.</div></div><div><h3>Results</h3><div>Significant differences were observed between the aGVHD and non-aGVHD groups in recipient age (<em>p</em> = 0.002), recipient weight (<em>p</em> = 0.02), donor age (<em>p</em> = 0.01), allele mismatch (<em>p</em> = 0.01), antigen mismatch (<em>p</em> = 0.01), and recipient CMV status (<em>p</em> = 0.04). Feature importance analyses using Random Forest (RF) and Boruta identified recipient age, weight, and donor age as the most influential predictors of aGVHD. Logistic Regression (LR) highlighted recipient Rh-positive status and donor blood group B as additional relevant factors, offering a complementary perspective. These findings may assist in risk assessment and the development of preventive strategies for aGVHD.</div></div><div><h3>Conclusion</h3><div>Machine learning methods effectively identified important predictors of aGVHD, demonstrating their potential to improve post-HCT care and preventive protocols. Our results underscore the complex aGVHD etiology, suggesting the involvement of various factors in its development. Further studies should focus on integrating these findings into the clinical practice to enhance patient outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102318"},"PeriodicalIF":1.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337707","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":"Macrophage polarization in organ transplantation rejection and targeted therapeutic strategies","authors":"Changqing Qu ,&nbsp;Yi Chen ,&nbsp;Xiaoyu Xu ,&nbsp;Xianduo Li ,&nbsp;Dongdong Chen ,&nbsp;Wenzhi Du ,&nbsp;Minrui Zhang ,&nbsp;Zhe Yang ,&nbsp;Jianning Wang","doi":"10.1016/j.trim.2025.102316","DOIUrl":"10.1016/j.trim.2025.102316","url":null,"abstract":"<div><div>Organ transplantation improves survival and quality of life in end-stage organ failure, but rejection remains a key barrier to long-term graft success. While current immunosuppression primarily targets adaptive immunity, its limitations and side effects necessitate alternative therapeutic strategies. Macrophages infiltrate grafts extensively, which are involved in antigen presentation function, ischemia-reperfusion injury, and both acute and chronic rejection processes. Notably, their polarization toward an anti-inflammatory phenotype may alleviate rejection and potentially contribute to graft immune tolerance. In this review, we will give an overview on macrophage phenotypes and their functional diversity in allograft rejection. Also, we will discuss emerging strategies to modulate macrophage polarization, including therapies exploiting their dual regulatory capacity, nanoparticle-based targeting systems, gene therapies, and microRNA-mediated regulation. A deeper understanding of macrophage biology in transplantation could enable more sophisticated anti-rejection approaches, whose integration with conventional immunosuppression may ultimately enhance long-term graft outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102316"},"PeriodicalIF":1.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329993","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 and safety of everolimus with reduced tacrolimus versus standard tacrolimus in liver transplant recipients: A systematic review and meta-analysis of randomized controlled trials","authors":"Akash Kumar ,&nbsp;Mateen Ahmad ,&nbsp;Amna Hussain ,&nbsp;Khadija Mohib ,&nbsp;Muhammad Asjad Saleem ,&nbsp;Muhammad Saad ,&nbsp;Muhammad Ansab ,&nbsp;Ram ,&nbsp;Pinkey Kumari ,&nbsp;Nisha Kumari","doi":"10.1016/j.trim.2025.102317","DOIUrl":"10.1016/j.trim.2025.102317","url":null,"abstract":"<div><h3>Background</h3><div>Liver transplantation (LT) requires immunosuppression to prevent rejection while minimizing adverse effects. Tacrolimus (TAC) is standard but linked to nephrotoxicity and leukopenia. Everolimus (EVR) with reduced-dose TAC (rTAC) offers a potential alternative, potentially improving safety while preserving efficacy.</div></div><div><h3>Objectives</h3><div>To compare everolimus with reduced-dose tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) in liver transplant recipients, assessing composite efficacy as the primary outcome, with graft loss, peripheral edema, mortality and evaluating safety via incidence of adverse events.</div></div><div><h3>Methods</h3><div>PubMed, Cochrane Library, and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> were systematically searched from inception until 1st March 2025. Randomized controlled trials (RCTs) comparing everolimus with reduced-dose tacrolimus (EVR + rTAC) versus standard tacrolimus (TAC) in liver transplant (LT) recipients were included. A random-effects model was used for meta-analysis to calculate pooled risk ratios with 95 % confidence intervals (CI).</div></div><div><h3>Results</h3><div>A total of seven studies encompassing 1853 liver transplant recipients (EVR + rTAC: 1167; sTAC: 1174) were included. EVR + rTAC significantly reduced the risk of treated biopsy-proven acute rejection (tBPAR) compared to sTAC (RR: 0.67; 95 % CI: 0.47–0.94; <em>p</em> = 0.02; I² = 1 %). Renal function, assessed by estimated glomerular filtration rate (eGFR), was significantly better in the EVR + rTAC group (MD: 8.41; 95 % CI: 2.37–14.44; <em>p</em> = 0.006; I² = 86 %). Additionally, EVR + rTAC was associated with a significantly higher risk of peripheral edema (RR: 1.56; 95 % CI: 1.25–1.95; <em>p</em> &lt; 0.0001; I² = 0 %) and leukopenia (RR: 2.87; 95 % CI: 1.99–4.13; <em>p</em> &lt; 0.00001; I² = 0 %).</div><div>No significant differences were observed between the EVR + rTAC and sTAC groups regarding the composite efficacy outcome (RR: 0.79; 95 % CI: 0.62–1.00; <em>p</em> = 0.05; I² = 0 %), graft loss (RR: 1.25; 95 % CI: 0.73–2.14; <em>p</em> = 0.41; I² = 0 %), mortality (RR: 1.30; 95 % CI: 0.87–1.96; <em>p</em> = 0.20; I² = 0 %), or the incidence of serious adverse events (RR: 1.03; 95 % CI: 0.94–1.12; <em>p</em> = 0.52; I² = 79 %). Furthermore, no significant differences were noted regarding diarrhea, abdominal pain, headache, or hypertension.</div></div><div><h3>Conclusion</h3><div>Everolimus with reduced-dose tacrolimus (EVR + rTAC) showed comparable efficacy to standard tacrolimus, with no significant differences in graft loss or mortality. It significantly reduced the risk of acute rejection and improved renal function (higher eGFR) but increased the risk of leukopenia and peripheral edema. Further studies are needed to optimize this renal-sparing regimen.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102317"},"PeriodicalIF":1.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329972","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":"Enhancement of allograft acceptance by combined dexmedetomidine and rapamycin","authors":"Chen-Fang Lee ,&nbsp;Chih-Hsien Cheng ,&nbsp;Hui-Hsin Chuang ,&nbsp;Hao-Chien Hung ,&nbsp;Wei-Chen Lee ,&nbsp;Hsiang-Sheng Wang","doi":"10.1016/j.trim.2025.102313","DOIUrl":"10.1016/j.trim.2025.102313","url":null,"abstract":"<div><h3>Background</h3><div>Dexmedetomidine, an α2-adrenoceptor agonist, is known for its sedative effects and unique pharmacological mechanism. Research increasingly emphasizes its potential to modulate immune responses. Further investigation is needed to fully understand how dexmedetomidine influences T cell differentiation and its potential synergy with tolerance-promoting agents. This study aims to explore a new approach to enhance allograft acceptance by combining dexmedetomidine with the mTOR inhibitor rapamycin.</div></div><div><h3>Methods</h3><div>The effects of both drugs on T cell proliferation, regulatory T cell preservation, and allograft survival were examined through both in vitro and in vivo animal experiments, including a fully MHC-mismatched mouse skin transplantation model. The study also evaluated the effect of combined drugs on immune memory via retransplantation surgery.</div></div><div><h3>Results</h3><div>Our data demonstrate that combining dexmedetomidine with rapamycin effectively inhibits T cell proliferation. This combination also increases the frequency of regulatory T cells, thereby preserving immune regulation. Furthermore, dual therapy significantly extends the median survival time (MST) of the skin compared to dexmedetomidine, or rapamycin alone or no treatment (20 vs. 12 days, <em>p</em> &lt; 0.001; 20 vs. 16 days, <em>p</em> &lt; 0.05; 20 vs. 7 days, <em>p</em> &lt; 0.0001). Similarly, mice treated with the combination therapy have notably prolonged MST of the second allogenic graft, compared to no treatment (11 days versus 7.5 days, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Our findings highlight the potential of combining dexmedetomidine with mTOR inhibitors to enhance graft acceptance and reduce memory responses.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102313"},"PeriodicalIF":1.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309318","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":"Hemophagocytic Lymphohistiocytosis with onset of mental and behavioral disorders following allogeneic hematopoietic stem cell transplantation: A case report","authors":"Heng Liu,&nbsp;Yaozhu Pan,&nbsp;Wu Tao,&nbsp;Dongfeng Mao,&nbsp;Hongjuan Tian,&nbsp;Feng Xue,&nbsp;Miao He","doi":"10.1016/j.trim.2025.102314","DOIUrl":"10.1016/j.trim.2025.102314","url":null,"abstract":"<div><div>Hemophagocytic lymphohistiocytosis (HLH) is a rare but highly fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with central nervous system involvement (CNS-HLH) being exceptionally uncommon in adults and posing significant diagnostic challenges. This report details a 24-year-old male with acute myeloid leukemia (AML-M5) who developed CNS-HLH on +50 day after haploidentical allo-HSCT. The patient achieved complete donor chimerism post-transplant with no active infections but subsequently presented with acute neuropsychiatric symptoms, including short-term memory impairment, hypersomnia, reduced verbal output, and psychomotor retardation, rapidly progressing to coma. Laboratory findings revealed pancytopenia, hyperferritinemia (4301 μg/L), hypertriglyceridemia, and elevated CD8⁺ T lymphocytes (58 %). Cerebrospinal fluid analysis showed increased pressure (220 mmH₂O) and markedly elevated protein (1350.3 mg/L), while cranial MRI demonstrated bilateral hippocampal and amygdaloid hyperintensities. Bone marrow examination confirmed hemophagocytosis, fulfilling the HLH-2004 criteria and modified post-HSCT HLH diagnostic criteria for secondary HLH. Despite aggressive interventions—high-dose methylprednisolone, intravenous immunoglobulin, plasma exchange, and ruxolitinib combined with intrathecal therapy—the patient remained comatose and succumbed to multi-organ failure. This case underscores the unique clinical trajectory of post-HSCT CNS-HLH, where neuropsychiatric manifestations precede classical hematologic abnormalities and conventional immunosuppressive therapies exhibit limited efficacy. The findings emphasize the imperative for heightened clinical suspicion of HLH in transplant recipients with unexplained neurological deterioration accompanied by progressive cytopenias and biomarker derangements. Furthermore, this report highlights the urgent need for optimized early diagnostic strategies and targeted therapeutic approaches for CNS-HLH. The case provides critical insights into the clinical management and mechanistic understanding of post-transplant HLH.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102314"},"PeriodicalIF":1.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145303680","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":"Linking autophagy to endothelial cell immunogenicity in transplant-associated ischemia-reperfusion injury","authors":"Meredith E. Taylor ,&nbsp;Dinesh Jaishankar ,&nbsp;Krishnaraju Madavaraju ,&nbsp;Simseok A. Yuk ,&nbsp;Kaijie Zhang ,&nbsp;Hongzhang Mei ,&nbsp;Connor W. Lantz ,&nbsp;Luisa H. Andrade da Silva ,&nbsp;Yu Min Lee ,&nbsp;Jacqueline A. Burke ,&nbsp;Carl Atkinson ,&nbsp;Bowen Wang ,&nbsp;Evan A. Scott ,&nbsp;Satish N. Nadig","doi":"10.1016/j.trim.2025.102315","DOIUrl":"10.1016/j.trim.2025.102315","url":null,"abstract":"<div><h3>Background</h3><div>Cold storage (CS) and ischemia-reperfusion injury (IRI) are inevitable consequences of heart transplantation (HTx), primarily affecting the microvascular endothelial cells (ECs) of donor hearts. The nutrient deprivation and oxidative stresses sustained by ECs during CS and IRI activate and trigger alloimmune recognition. ECs adapt to these conditions by utilizing autophagy to maintain cellular homeostasis. Whether autophagy plays a role in EC activation and immunogenicity during CS and IRI in HTx remains unknown.</div></div><div><h3>Methods</h3><div>Autophagy in murine microvascular cardiac endothelial cells (MCEC) was modulated by genetic (knockout of the autophagy-related gene 5 (Atg5) by CRISPR/Cas9 technology) or pharmacological (rapamycin to induce autophagy and chloroquine to inhibit autophagy) approaches or by nanocarriers encapsulating rapamycin. MCECs were subjected to a previously established cold storage-warm reperfusion (CS-WR) model to mimic CS and IRI. We evaluated a) changes in autophagy by immunoblotting and confocal imaging, b) MCEC activation via pro-inflammatory cytokine and chemokine secretion by ELISA, and c) MCEC immunogenicity by determining T-cell activation in EC-T-cell co-cultures with MCEC-sensitized CD8⁺ T cells. The human relevance of EC autophagy was demonstrated by reanalyzing a recently published single-nucleus RNA sequencing dataset obtained from baseline and cold-preserved human donor hearts.</div></div><div><h3>Results</h3><div>Autophagy was reduced in MCECs when subjected to CS alone in organ preservation solution and increased early on during WR. The absence of the autophagic machinery in Atg5^−/− MCECs significantly increased MCEC activation and immunogenicity, while pharmacological induction of autophagy with rapamycin significantly mitigated this effect. Additionally, treating MCECs with an organ preservation solution supplemented with rapamycin-loaded nanocarriers during hypothermic CS demonstrated a protective effect in mitigating MCEC immunogenicity. Reanalysis of the single-nucleus RNA sequencing dataset in EC subclusters revealed that cold storage induced an activated EC state characterized by reduced expression of autophagy-related genes, aligning with our in vitro findings.</div></div><div><h3>Conclusions</h3><div>A novel role of autophagy in MCEC immunogenicity during CS and IRI is implicated. A viable preconditioning approach has also been demonstrated to bolster MCEC autophagy with nanocarriers during CS and mitigate its immunogenicity.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102315"},"PeriodicalIF":1.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287165","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":"Immunomodulation in post-transplant diabetes mellitus: Challenges and management","authors":"Hanan Maoz,&nbsp;Amir Elalouf","doi":"10.1016/j.trim.2025.102304","DOIUrl":"10.1016/j.trim.2025.102304","url":null,"abstract":"<div><div>Solid organ transplantation (SOT) in diabetic patients presents unique challenges in balancing immunosuppression, glycemic control, and the risk of infection. Post-transplant diabetes mellitus (PTDM) affects 10 %–40 % of transplant recipients, with immunosuppressive therapies such as corticosteroids and calcineurin inhibitors (CNIs) contributing to insulin resistance and impaired beta-cell function. This review critically examines immunomodulation strategies in diabetic SOT recipients, focusing on optimizing immunosuppressive therapy while mitigating hyperglycemia-related complications. Early glycemic control through insulin therapy, followed by a transition to oral hypoglycemic agents such as metformin, GLP-1 receptor agonists, and DPP-4 inhibitors, has proven effective in reducing PTDM and enhancing long-term transplant outcomes. Alternative immunosuppressive strategies, including belatacept-based regimens and switching from tacrolimus to cyclosporine, offer promising methods to lower PTDM incidence while preserving graft survival. Personalized immunosuppressive regimens tailored to an individual's metabolic risks further improve patient outcomes. Emerging strategies, such as monoclonal antibodies, mesenchymal stem cell therapy, and localized immunomodulation, hold promise for enhancing immune balance while mitigating metabolic complications. A multidisciplinary team involving endocrinologists, transplant surgeons, and diabetes specialists is essential for comprehensive management. Additionally, routine screening for new-onset diabetes after transplantation (NODAT) and early interventions are vital to prevent long-term complications. Despite advancements, gaps remain regarding the long-term metabolic effects of immunosuppressive agents, the optimal timing for transitioning from insulin to oral therapy, and the role of new immunomodulatory treatments. Future research should focus on personalized therapeutic approaches that combine immunosuppressive and metabolic management to improve graft function and patient health. This review highlights the importance of a balanced approach to immunosuppression for diabetic transplant recipients, aiming to enhance survival rates and quality of life.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102304"},"PeriodicalIF":1.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287136","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":"Hematopoietic stem cell transplantation across ABO compatibility barrier in HLA genoidentical related donor: Is it an unfavorable factor for overall survival (OS) in Tunisian patients?","authors":"Mohamed Hichem Sellami ,&nbsp;Yesmine Boughzala ,&nbsp;Eya Ghazouani ,&nbsp;Nour Ben Abdeljelil ,&nbsp;Ines Turki ,&nbsp;Wafa Aissa ,&nbsp;Manel Chaabane ,&nbsp;Houda Kaabi ,&nbsp;Tarek Ben Othman ,&nbsp;Slama Hmida","doi":"10.1016/j.trim.2025.102311","DOIUrl":"10.1016/j.trim.2025.102311","url":null,"abstract":"<div><div>Benchmarking of survival following Hematopoietic Stem Cell Transplantation (HSCT) is very useful in the field of transplant medicine. It has been reported that decreased survival rates after HSCT may be affected by the ABO mismatch in some cases. In this study, we aim to assess this relationship in a Tunisian cohort of adult patients who have received HSCT from HLA genoidentical related donors.</div><div>A total of 147 patients and their 147 respective related donors, were retrospectively analyzed in this study. HLA and ABO antigens typing was performed according to established routine methods. Overall Survival (OS) was measured from the date of the HSCT until death from any cause or the last follow-up examination. OS in the ABO-matched group and the ABO-mismatched groups was accessed using mean survival time, comparison of survival curves (using the Logrank test) and calculation of the hazard ratios (HR) with 95 % confidence interval (CI).</div><div>The comparison of survival curves showed no significant difference (chi2 = 0.898, <em>p</em> = 0.825) in the OS between the ABO-compatible graft recipients and those who are incompatible (Bidirectional, Major or Minor incompatibility). Survival analysis with HR showed no difference in mortality between the fourth targeted subgroups. This is the same result even when the source of the hematopoietic graft, i.e., peripheral blood stem cells (PBSCs) or bone marrow (BM) stem cells, was taken into consideration.</div><div>It is very likely that there is no effect of ABO mismatching on OS in Tunisian adult recipients of HSCs. This result is in good agreement with that of other recent reports that failed to establish a significant relationship between ABO incompatibility and OS after the HSCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102311"},"PeriodicalIF":1.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275787","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":"Transplant outcomes after de novo donor specific antibody (DSA) development correlate with persistence of DSA","authors":"A. Jaffer ,&nbsp;O. Shaw ,&nbsp;D. Stringer ,&nbsp;A. Dorling ,&nbsp;S. Shah","doi":"10.1016/j.trim.2025.102312","DOIUrl":"10.1016/j.trim.2025.102312","url":null,"abstract":"<div><h3>Background</h3><div>The OuTSMART trial confirmed <em>de novo</em> DSAs were associated with an increased risk of graft loss and rejection. In this post-hoc analysis, outcomes were analysed in 132 patients who had a DSA at the point of randomisation and compared between patients who had persistent DSA (DSA+/+) with those in whom the DSA was not detected on subsequent samples (DSA+/−).</div></div><div><h3>Methods</h3><div>Serial serum samples were collected post-enrolment until 2016. Those who had their final visit after 2018, had repeat HLA antibody testing ≥32 months post-randomisation. 115 of the 132 DSA+ patients had 2 or more samples available for analysis. 39/115 patients were persistently DSA+ and in 76/115 the DSA became undetectable at 12–32 months post enrolment.</div></div><div><h3>Results</h3><div>Both groups were well matched in sex, ethnicity, immunosuppression, and DSA status at transplant. The total Mean Fluorescence Intensity (MFI) of baseline DSA was significantly higher in the DSA+/+ <em>vs</em> DSA+/− (11,568 v 6518, <em>P</em> &lt; 0.01) with a predominance of class II HLA. Significantly higher rates of antibody mediated rejection (ABMR) and death censored graft failure (GF) were seen in DSA+/+ <em>vs</em> in DSA+/− (15.4 % v 2.6 %, <em>P</em> = 0.02 and 20.5 % v 6.6 %, <em>P</em> = 0.03 respectively). In Cox regression analysis, persistent DSA and having both HLA classes were associated with increased risk of ABMR (HR 6.05, CI 1.2–30.0, P = 0.03 and HR 14.7, CI 1.33–162, P = 0.03 respectively). Additionally, persistent DSA was associated with higher GF rates (HR 3.4, 1.1–10.4, P = 0.03).</div></div><div><h3>Conclusions</h3><div>Persistent <em>de novo</em> DSA, after kidney transplantation, is associated with higher MFI and increased risk of ABMR and GF.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102312"},"PeriodicalIF":1.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267894","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":"HLA-specific platelet trasfusion as part of desensitization strategy in patients with donor-specific anti-HLA antibodies before stem cell transplantation","authors":"Giuliana Lando ,&nbsp;Roberto Crocchiolo ,&nbsp;Giorgia Cornacchini ,&nbsp;Giulia Di Maggio ,&nbsp;Cristina Garanzini ,&nbsp;Giovanni Grillo ,&nbsp;Benedetta Mazzi ,&nbsp;Silvano Rossini ,&nbsp;Michela Tassara","doi":"10.1016/j.trim.2025.102310","DOIUrl":"10.1016/j.trim.2025.102310","url":null,"abstract":"<div><div>The presence of donor-specific anti-HLA antibodies (DSAs) in patients who are candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a recognized risk factor for delayed engraftment and mortality. In the absence of an alternative donor, patient desensitization is indicated to reduce or eliminate DSAs; however, harmonization among transplant centers remains insufficient and reduction of DSAs is sometimes unsuccessful. Here, we present the feasibility and results of our recent monocenter experience on nine immunized HLA class I DSA+ patients undergoing pre-transplant desensitization using HLA-specific platelet transfusion, as a means of antibody adsorption through platelets expressing the same HLA specificities targeted by DSAs. All allo-HSCTs were from HLA-mismatched donors, both unrelated or related haploidentical. The approach appeared safe for donors and patients and potentially useful in mitigating the detrimental impact of class I DSAs, with successful engraftment observed in two of four patients with MFI &gt; 10,000 and in all patients with MFI &lt;10,000. Until harmonized and more risk-adapted desensitization strategies become available, sharing inter-center experiences between clinical and transfusion units will likely improve the management of hyperimmunized patients and enhance the availability of emerging desensitizing strategies.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102310"},"PeriodicalIF":1.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275765","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}