Transplant immunology最新文献

{"title":"mRNA vaccine for human cytomegalovirus in immunocompromised hosts: An immunoinformatics approach","authors":"Muhammad Zeeshan Ahmed ,&nbsp;Sana Dilbar ,&nbsp;Syeda Masooma Zahra Bukhari ,&nbsp;Zareena Ali ,&nbsp;Binyamin Wattoo ,&nbsp;Sayra Tariq ,&nbsp;Zeeshan Mutahir ,&nbsp;Noreen Samad","doi":"10.1016/j.trim.2025.102342","DOIUrl":"10.1016/j.trim.2025.102342","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals, including transplant recipients, neonates, and patients with immunosuppression. Despite extensive research, no effective vaccine exists—especially one leveraging mRNA technology. This study aimed to design a safe and immunogenic multi-epitope mRNA vaccine against HCMV using a comprehensive immunoinformatics approach. Glycoprotein B (gB), a highly conserved and immunodominant antigen, was selected as the vaccine target. B-cell, MHC-I, and MHC-II epitopes were predicted based on their antigenicity, immunogenicity, non-allergenicity, and non-toxicity. Of these, three B-cell binding epitopes, 3 MHC-II, and 4 MHC-I binding epitopes of T-cells, along with a toll-like receptor (TLR) agonist and an MHC I- targeting domain (MITD), were rationally assembled to design an mRNA vaccine construct (HCMVV). This construct was evaluated for physicochemical properties, population coverage, structural stability, interactions with innate receptors (TLR 2/4), and simulated immune responses. The vaccine showed high stability and favorable expression profiles, including ten conserved epitopes with broad MHC coverage, especially in South Asian populations. Docking studies indicated a stronger binding affinity for HCMVV–TLR 4 (− 19. 6 kcal/mol) compared to HCMVV–TLR 2 (− 14. 1 kcal/mol), characterized by high affinity and structural complementarity. Normal mode analysis confirmed complex stability, with average deformability per atom index for HCMVV, HCMVV–TLR 2, and HCMVV–TLR 4. Furthermore, molecular dynamics simulation (MDS) over 100 ns using GROMACS confirmed the stability of HCMVV–TLR2 and HCMVV–TLR4 complexes, with RMSD values below 2 Å (HCMVV–TLR4 more stable at &lt;1.3 nm), low RMSF indicating rigidity (except specific flexible regions in TLR4), consistent hydrogen bonds (400–540), compact RoG (&lt;2.7 nm for TLR4), stable SASA (370–430 nm² with slight reduction in TLR4), and PCA revealing dominant conformational motions. Immune simulations predicted strong IgG and T-cell responses, as well as memory formation and efficient antigen clearance. This study introduces a promising mRNA vaccine candidate against HCMV with substantial immunogenic potential, especially for high-risk groups. However, experimental validation, including in vitro expression, in vivo immunogenicity, and protective efficacy studies, is essential to translate these computational findings into clinical applications.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102342"},"PeriodicalIF":1.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744822","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":"Impact of induction agent selection on rejection, allograft function, and survival in kidney transplant recipients","authors":"Mohamad Saria Aldarwish ,&nbsp;Wassim Toomah ,&nbsp;Amro Idilbi ,&nbsp;Roaa Ghanem ,&nbsp;Mohamed Hussam Hallak ,&nbsp;Alaa Alhalabi ,&nbsp;Alia Alhassoun ,&nbsp;Mohammad Mawaldi ,&nbsp;Mohamad Amir Balloura ,&nbsp;Emily C. Craver ,&nbsp;Tambi Jarmi","doi":"10.1016/j.trim.2025.102341","DOIUrl":"10.1016/j.trim.2025.102341","url":null,"abstract":"<div><h3>Background</h3><div>Kidney allograft rejection, driven by the recipient's immune response to non-self-HLA, remains a key barrier to kidney allograft survival. Induction therapy seeks to suppress early alloimmunity and reduce rejection. This study compares Basiliximab, Alemtuzumab, and Thymoglobulin in terms of acute rejection, kidney allograft function, and patients' survival.</div></div><div><h3>Methods</h3><div>A retrospective, single-center cohort study was conducted on 917 kidney transplant recipients between January 2019 and December 2023. Patients were stratified into Alemtuzumab (<em>n</em> = 337), Basiliximab (<em>n</em> = 300), and Thymoglobulin (<em>n</em> = 280) groups. The primary outcome was biopsy-proven acute rejection within the first 12 months post-transplant. Secondary outcomes included kidney allograft function. Kaplan-Meier survival analysis was performed to assess survival differences across groups.</div></div><div><h3>Results</h3><div>There was no statistically significant difference in acute rejection rates within the first 12 months among the three induction groups: Basiliximab (15 %), Thymoglobulin (14 %), and Alemtuzumab (9 %) (<em>p</em> = 0.16). Median creatinine clearance showed significant differences, with higher values in the Thymoglobulin (57.0 mL/min) and Alemtuzumab (56.0 mL/min) groups compared to the Basiliximab group (48.0 mL/min) (<em>p</em> = 0.003). Kaplan-Meier survival analysis demonstrated a statistically significant difference in patient survival over the 5-years follow-up period, with the highest survival observed in the Alemtuzumab group, followed by Thymoglobulin and then Basiliximab (<em>p</em> = 0.0067).</div></div><div><h3>Conclusion</h3><div>Basiliximab showed similar acute rejection rates to lymphocyte-depleting agents, suggesting it is not inferior in preventing early rejection when used for a selected group of patients. These findings support the need for further multi-center studies to better define optimal induction strategies and adapt therapy to individual patient profiles.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102341"},"PeriodicalIF":1.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744824","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":"Human leukocyte antigen-C*08 increases the risk of BK virus viremia in kidney transplant recipients","authors":"Marie-Pier Thivierge,&nbsp;Stéphanie Béland,&nbsp;Olivier Désy,&nbsp;Sacha A. De Serres","doi":"10.1016/j.trim.2025.102340","DOIUrl":"10.1016/j.trim.2025.102340","url":null,"abstract":"<div><div>BK virus (BKV) infection can cause graft loss in kidney transplant recipients. Several factors increase the risk of infection, including high level of immunosuppression, older age, and human leukocyte antigen (HLA) mismatch. The primary function of the major histocompatibility complex (HLA in human) is the presentation of peptides that originated from foreign or self-antigens to T cells to trigger an immune response, such as during infections. Identifying HLA genotypes that can influence the course of BKV infection could allow for stratifying patients according to their risk of developing the infection, thus personalizing the use of immunosuppressants. We conducted a retrospective study in a cohort of 1302 kidney transplant recipients, of whom 243 (19 %) developed BKV viremia. Clinical data and HLA genotype were evaluated for associations with BKV viremia. Among the 51 HLA genotypes analyzed, exploratory analysis revealed that patients expressing the HLA-C*08 genotype had a high risk of developing BKV viremia (<em>p</em> = 0.04). Using multivariate analyses adjusted for clinical variables that differed between patients with and without BK viremia (age and number of HLA-B mismatches), we confirmed that the HLA-C*08 genotype was associated with BK viremia. HLA-C*08, expressed by a sizeable proportion of the patients (82 individuals, or 6.3 % of the cohort), increased the risk of BKV viremia by 1.61 fold (<em>p</em> = 0.03). The HLA genotype may be useful in managing screening strategies for BKV in transplant recipients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102340"},"PeriodicalIF":1.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695893","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":"Relation between monocyte to high-density lipoprotein cholesterol ratio and prognosis in recipients after liver transplantation","authors":"Serafettin Okutan ,&nbsp;Hasan Saritas ,&nbsp;Serdar Saritas ,&nbsp;Semra Bulbuloglu ,&nbsp;Hüseyin Guneş","doi":"10.1016/j.trim.2025.102331","DOIUrl":"10.1016/j.trim.2025.102331","url":null,"abstract":"<div><h3>Background</h3><div>The end-stage liver diseases require liver transplantation as the life-saving solution. It is known that monocytes/macrophages and high-density lipoprotein cholesterol (HDL<img>C) have important contributions to the development of hepatic inflammation and oxidative stress before liver transplantation. However, the effect of monocyte/HDL-C ratio (MHR) on clinical progression and outcome in the post-transplant period are not fully understood. Our hypothesis is that the MHR value may be associated with poor vs. good outcomes after liver transplantation.</div></div><div><h3>Methods</h3><div>In our retrospective study, we included 464 liver transplant recipients. Patients' data were extracted from electronic and other paper records in our teaching/research hospital. The MHR values and other blood parameters (creatinine, total protein, albumin, etc.) were expressed as a mean and standard deviation, which were analyzed by the Pearson correlation test. The relationship between graft dysfunction and MHR was determined by ROC curve analysis.</div></div><div><h3>Results</h3><div>The mean age of liver transplant recipients was 45.8 ± 13.7 years. Nineteen percent of patients had liver failure due to Alcoholic Fatty Liver Disease (AFLD) and 34.5 % had liver failure due to hepatitis B virus. At the end of 3 months after liver transplantation, 84.5 % of liver transplant recipients were alive, 5.8 % experienced graft rejection and 5.17 % had an infection. There was a statistically significant improvement in total protein, albumin, liver function tests, and serum creatinine values of the survivors (all <em>p</em> &lt; 0.05). The MHR levels were significantly higher in patients who died after transplantation in comparison to those who survived before and after liver transplantation and these differences were statistically significant (<em>p</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>The increased MHR values of recipients after liver transplantation correlated with their risk of survival. Furthermore, the MHR value increased with increased MELD score and the number of days of hospitalization and was not affected by gender and age. MHR was higher in patients with chronic diseases. Patients with high MHR before and after transplantation should be monitored more closely in the perioperative period.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102331"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614841","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":"Temporal dynamics of cPRA levels and their categorical impact on waitlist longevity in Ecuadorian kidney transplant candidates: A 2011–2022 Nationwide cohort analysis","authors":"David Garrido ,&nbsp;Verónica Jeréz ,&nbsp;Jorge Huertas","doi":"10.1016/j.trim.2025.102329","DOIUrl":"10.1016/j.trim.2025.102329","url":null,"abstract":"<div><div>Background: Chronic kidney disease is a major public health concern for which kidney transplantation offers the best survival benefit. Patients with high calculated panel-reactive antibody (cPRA) levels often face extended waiting times owing to donor compatibility challenges.</div><div>Methods: We conducted a descriptive, cross-sectional analysis of all 724 kidney transplant candidates on Ecuador's national waiting list between 2011 and 2022, using anonymized INDOT data. cPRA values were obtained with solid-phase, bead-based luminometric assays. We applied descriptive statistics, Joinpoint regression to assess temporal trends, Spearman correlation for cPRA versus waiting time, chi-square tests for categorical comparisons, and logistic regression to estimate odds ratios (ORs) for prolonged waiting time (&gt;5 years).</div><div>Results: Overall, 166 candidates (22.9 %) had cPRA ≥20 %. Of these, 86 (51.8 %) exhibited cPRA ≥75 %. The number of sensitized patients with cPRA ≥75 % rose from one in 2011 to nineteen in 2022 (annual percent change 10.4 %). Median waiting time was 54.5 months for candidates with cPRA ≥75 % versus 51.5 months for those with cPRA 20–74 %; there was no linear correlation between cPRA and waiting time (ρ = 0.11, <em>p</em> = 0.18). However, candidates with cPRA ≥75 % were more likely to wait &gt;5 years than those below this threshold (44.2 % vs. 25.0 %; OR 2.38; <em>p</em> = 0.01), and a similar pattern was observed for candidates with cPRA ≥70 % (OR 2.98; <em>p</em> = 0.003).</div><div>Conclusion: The proportion of highly sensitized candidates has increased substantially between 2011 and 2022. Patients with cPRA levels ≥75 % were associated with prolonged waitlist time to obtain a kidney transplant. Prospective studies are warranted to explore underlying mechanisms and inform allocation strategies.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102329"},"PeriodicalIF":1.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651724","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":"Novel, short-course, low-dose total lymphoid irradiation (TLI) post heart transplant for recalcitrant rejection – A single centre experience","authors":"Felicity Lee ,&nbsp;B.N. Clare Fazackerley ,&nbsp;Tee S. Lim ,&nbsp;Lloyd D'Orsogna ,&nbsp;Jon Downing ,&nbsp;Linh Truong ,&nbsp;Amit Shah ,&nbsp;Jay Baumwol ,&nbsp;Kaitlyn Lam ,&nbsp;James Lambert ,&nbsp;Peter Dias ,&nbsp;Faith Njue ,&nbsp;Lawrence Dembo","doi":"10.1016/j.trim.2025.102333","DOIUrl":"10.1016/j.trim.2025.102333","url":null,"abstract":"<div><h3>Background</h3><div>A previous small study (2007) of patients who received short-course, low-dose total lymphoid irradiation (sTLI) as treatment for recalcitrant cardiac rejection post-heart transplantation (HTx) reported good treatment compliance without significant toxicities and improvement in rejection frequency. We conducted a retrospective analysis, evaluating longer-term outcomes in this patient cohort.</div></div><div><h3>Methods and results</h3><div>We reviewed the medical records of 21 HTx recipients (mean age ± std. 43.7 ± 12.8 years; 47.6 % female) who received sTLI between 2001 and 2023. Five patients were highly sensitized pre-HTx (calculated panel-reactive antibody &gt;80 %) and 8 patients received induction immunosuppression at time of HTx. Patients received 4.5Gy in four fractions over 4 consecutive days administered (<em>n</em> = 13 as an outpatient), at a median of 442 (IQR 47–966) days post-HTx. STLI was well-tolerated symptomatically with no persistent lymphopenias. Eleven patients had no further rejection. Ten patients had immediate rejection resolution with later rejection detected (median 401 [IQR 301–1569] days post-sTLI). Thirteen patients, mostly transplanted pre-2010, have deceased (median graft survival 7.6 years, mean follow-up 9.4 years). One patient died of metastatic colon cancer. There were no haematological malignancies. Two patients received a second sTLI course and subsequent re-HTx.</div></div><div><h3>Conclusions</h3><div>We report the largest case series of patients who received sTLI post-HTx. STLI is well-tolerated, with resolution of immediate recalcitrant rejection in all patients and resolution of rejection in the longer term in 52 %. STLI is a possible alternative option for patients with cardiac rejection refractory to routine, augmented immunotherapy. Further larger studies are required to assess the longer-term efficacy and safety of this treatment.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102333"},"PeriodicalIF":1.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655374","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":"Conversion to belatacept-based immunosuppression as a calcineurin sparing regimen in lung transplant: A multi-institutional retrospective study","authors":"Moustafa Younis ,&nbsp;Cecelia M. Miller ,&nbsp;Christopher I. Mederos ,&nbsp;Ariana Ishaq ,&nbsp;Pooja Kumar ,&nbsp;Biplab Saha ,&nbsp;Cynthia Gries ,&nbsp;Victoria Reams ,&nbsp;Vaidehi Kaza ,&nbsp;Srinivas Bollineni ,&nbsp;Fernando Torres ,&nbsp;Mohammad A. Aladaileh ,&nbsp;Mindaugas Rackauskas ,&nbsp;Irina Timofte ,&nbsp;Amir Emtiazjoo","doi":"10.1016/j.trim.2025.102330","DOIUrl":"10.1016/j.trim.2025.102330","url":null,"abstract":"<div><h3>Background</h3><div>Calcineurin inhibitor (CNI) related kidney dysfunction is common and associated with worse outcomes after lung transplantation (LTx). To mitigate that risk, belatacept use in a CNI-sparing regimen is an alternative in LTx. We aim to describe our experience using belatacept as a CNI-sparing regimen in LTx.</div></div><div><h3>Methods</h3><div>A multi-institutional retrospective review of LTx patients who received belatacept (1/2018–8/2023) was performed. The primary outcome is the change in estimated glomerular filtration rate (eGFR) after initiation of belatacept. Secondary outcomes were compared with a control group of patients transplanted during 1/2018–8/2023 that did not receive belatacept. Secondary outcomes include acute cellular rejection (ACR), denovo donor specific antibodies (DSA), antibody mediated rejection (AMR), infections, malignancy, chronic lung allograft dysfunction (CLAD) and mortality.</div></div><div><h3>Results</h3><div>A total of 170 LTx patients who received belatacept were included for the primary outcome. To investigate the secondary outcomes an additional 288 LTx controls were used. The median (IQR) eGFR at the time of belatacept initiation, six months, and one year post belatacept initiation was 43 (34–52), 46 (37–53) and 43 (36–53) mL/min/1.73 m2, respectively (<em>p</em> = 0.21). There was no significant difference in ACR, DSA, AMR, infections, malignancy, CLAD or mortality between both groups.</div></div><div><h3>Conclusions</h3><div>Belatacept CNI-sparing therapy was well tolerated and feasible in LTx recipients, with renal function appearing to stabilize over time and no apparent safety signal for acute rejection, infection, malignancy, CLAD, or mortality.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102330"},"PeriodicalIF":1.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655446","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":"Smart transplant+: A HyCARE hybrid AI–cloud framework for intelligent donor–recipient matching, workflow automation, and post-transplant optimization","authors":"Winner Pulakhandam ,&nbsp;Archana Chaluvadi ,&nbsp;Visrutatma Rao Vallu ,&nbsp;R. Padmavathy","doi":"10.1016/j.trim.2025.102332","DOIUrl":"10.1016/j.trim.2025.102332","url":null,"abstract":"<div><div>Organ transplantation is a life-saving medical intervention to reverse end-stage organ failure. Despite its life-saving potential, organ transplantation faces inefficiencies like organ shortages, long wait times, and rejection risks due to manual, clinically limited donor-recipient matching. The rapid growth of AI and cloud computing offers new opportunities to enhance organ transplantation. This study proposes Smart Transplant+, a HyCARE system enabling intelligent matching, decision-making, and process automation. The architecture leverages a huge Organ Transplant Dataset and the most advanced methods such as Feedforward Neural Networks and Genetic Algorithms to maximize donor-recipient matching. Gated Recurrent Units are utilized in pre-transplant risk prediction, and post-transplant care is augmented with real-time tracking by IoT-based wearable sensors. The system has been programmed using Python, along with software tools like TensorFlow for machine learning and AES encryption for secure data storage and transmission. The Smart Transplant+ system provides 95–98 % accuracy which is higher than existing methods in identifying suitable donors and recipients and the potential for successful transplantation, and greatly enhances organ transplant efficiency and success rate. This book illustrates the revolutionary potential of synergizing IoT, cloud technology, and AI to optimize transplant care and improve outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"94 ","pages":"Article 102332"},"PeriodicalIF":1.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640344","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":"Characteristics linking ischemia-reperfusion to chronic lung allograft dysfunction in lung transplantation: A single-cell bioinformatics analysis","authors":"Peng Zhang ,&nbsp;Zhendong Qiao ,&nbsp;Song Zhao ,&nbsp;Kai Wu","doi":"10.1016/j.trim.2025.102326","DOIUrl":"10.1016/j.trim.2025.102326","url":null,"abstract":"<div><h3>Background</h3><div>Lung transplantation offers a life-saving procedure to patients with end-stage lung diseases with 85–89 % one year and 60 % five-year survival rates. Lung transplants are complicated by early ischemia/reperfusion injury (IRI) and late chronic lung allograft dysfunction (CLAD). However, the cellular and molecular links between IRI and CLAD remain unclear.</div></div><div><h3>Materials and methods</h3><div>We integrated single-cell RNA-seq results from <span><span>GSE220797</span><svg><path></path></svg></span> and <span><span>GSE224210</span><svg><path></path></svg></span> data sets. After quality filtering, we performed Louvain clustering and UMAP visualization. We applied Augur method to prioritize cell populations by transcriptional responsiveness to IRI and CLAD. We also performed dynamic trajectory analyses to map pseudotemporal transitions. Pathway activity was characterized by differential expression analysis and module scoring. Intercellular communication was assessed using CellChat and MEBOCOST analyses. Regulon inference was performed with pySCENIC analysis.</div></div><div><h3>Results</h3><div>Overall, epithelial cells showed progressive metabolic suppression and activation of cuproptosis, a programmed cell death (PCD) triggered by excessive copper accumulation within cells. Club cells, found in the small airways of the lungs, exhibited developmental plasticity and predictive potential across IRI and CLAD conditions. Among myeloid populations, M1 proinflammatory (AM_M1TM) macrophages underwent macrophage-to-myofibroblast transition (MMT) and produced excessive extracellular matrix (ECM) supporting a network of proteins surrounding cells. Metabolite and cell–cell communication analyses revealed declining macrophage/epithelial metabolic crosstalk and differential signaling flux from normal through IRI to CLAD transition.</div></div><div><h3>Conclusions</h3><div>The integrated single-cell atlas delineates interaction of multiple cells and their signaling pathways linking IRI to CLAD processes. These findings require further verification through studies in animal models and clinical samples.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102326"},"PeriodicalIF":1.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514175","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":"Immune mediators as therapeutic targets in GvHD; cytokines, growth factors, chemokines, and co-stimulation /co-inhibition","authors":"Amir Rastegari ,&nbsp;Fatemeh Mohebbi","doi":"10.1016/j.trim.2025.102328","DOIUrl":"10.1016/j.trim.2025.102328","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and emerging allogeneic T cell–based immunotherapies offer curative potential for hematologic malignancies, solid tumors, and selected non-malignant disorders through graft-versus-tumor (GvT) and immune reconstitution effects mediated by donor immune cells. However, their clinical success is constrained by graft-versus-host disease (GvHD) and other immune-mediated toxicities resulting from donor–host alloreactivity. Therefore, a central challenge is to develop personalized, safer allogeneic cellular therapies that preserve potent anti-tumor and immune-restorative functions while minimizing tissue injury. This review integrates the current understanding of acute and chronic GvHD immunopathogenesis, covering cytokine and chemokine networks, growth-factor signaling, and co-stimulatory/co-inhibitory pathways, and links these mechanisms to therapeutic strategies for selective immune modulation. Drawing on translational insights, we propose a framework for next-generation allogeneic cell-based therapies that are precision-tuned to donor/recipient biology, advancing individualized anticancer and immune-reconstitution outcomes with improved safety.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102328"},"PeriodicalIF":1.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516906","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}