Transplant immunology最新文献

{"title":"Research on gene editing and immunosuppressants in kidney xenotransplantation","authors":"JiaJiao Luo,&nbsp;CongWen Bian,&nbsp;Min Liu,&nbsp;Yuan Fang,&nbsp;Li Jin,&nbsp;Rui Yu,&nbsp;HanFei Huang","doi":"10.1016/j.trim.2025.102184","DOIUrl":"10.1016/j.trim.2025.102184","url":null,"abstract":"<div><div>Gene-edited pig organ transplantation can solve the serious shortage of human donor organs. Currently, xenotransplantation is rapidly developing and has made significant breakthroughs. The use of GTKO (Gal knockout) pigs is an important step forward. The subsequent knockout of three genes combined with the transfer of immune-related genes effectively prolonged the survival time of non-human primate (NHP) transplantation in xenotransplantation. Due to the success of allogeneic kidney transplantation on NHP, this gene editing protocol was recently applied to clinical patients. Two patients underwent allogeneic kidney transplantation and survived for 51 days and 47 days. Exceeding the hyperacute rejection period proves that appropriate gene editing strategies and the combination of immunosuppressive agents contribute to the success of xenotransplantation. To further enhance the feasibility of pig kidney xenograft, this article mainly explores the effects of the NHP xenograft gene editing scheme and immunosuppressants on prolonging transplant survival time.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102184"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into the circ_0003489/let-7b-5p/GLUT1 axis and its possible role in multiple myeloma","authors":"Xiaoyan Wang ,&nbsp;Qinqin Yang ,&nbsp;Yuedi Wu","doi":"10.1016/j.trim.2024.102165","DOIUrl":"10.1016/j.trim.2024.102165","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) act as vital players in multiple myeloma (MM). Herein, we focused on the function of hsa_circ_0003489 (circ_0003489) in MM development and bortezomib (BTZ) resistance.</div></div><div><h3>Methods</h3><div>Relative RNA levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative protein levels were evaluated by Western blotting or immunohistochemistry (IHC). The 5′-ethynyl-2′-deoxyuridine (EdU) and cell colony formation (CF) assays were conducted for cell proliferation. Cell counting kit-8 assay was used to evaluate the BTZ resistance. Flow cytometry analysis was performed for cell apoptosis analysis. Glycolysis was determined by detecting the levels of ECAR, glucose consumption, and lactate production. Dual-luciferase reporter and RNA pull-down assays were carried out to analyze the relationships of circ_0003489 with let-7b-5p microRNA and glucose transporter 1 (GLUT1) glucose transporter protein. Xenograft models were conducted to assess the function of circ_0003489 in vivo.</div></div><div><h3>Results</h3><div>Indeed, as shown by qRT-PCR, bone marrow samples of MM patients showed an upregulation of circ_0003489 RNA in comparison to normal controls (<em>P</em> &lt; 0.0001). In in vitro experiments in MM cells, silencing of circ_0003489 repressed cell proliferation, BTZ resistance, and glycolysis. Furthermore, blocking circ_0003489 facilitated in vitro the apoptosis of MM cells. In vivo experiments showed that silencing circ_0003489 decreased tumor formation. Signaling experiments demonstrated that circ_0003489 sponged let-7b-5p microRNA and negatively regulated let-7b-5p microRNA expression. Loss of let-7b-5p microRNA ameliorated circ_0003489 silencing-mediated effects on MM cell malignant behaviors and BTZ resistance. Moreover, we showed that GLUT1 glucose transporter was targeted by let-7b-5p mircoRNA. GLUT1 enhancement reversed the repressive impacts of let-7b-5p upregulation on MM cell malignant behaviors and BTZ resistance.</div></div><div><h3>Conclusion</h3><div>We suggest that circ_0003489 RNA knockdown inhibited MM progression and reversed BTZ-induced resistance of MM growth by let-7b-5p microRNA regulated function of GLUT1 glucose transporter.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102165"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882852","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":"Tacrolimus-induced thrombotic microangiopathy (TMA) after heart and lung transplantation successfully treated with eculizumab","authors":"Zein Kattih ,&nbsp;Aldo Iacono ,&nbsp;Christina Saikus ,&nbsp;Michael Esposito ,&nbsp;Zachary Kon ,&nbsp;Maksim Korotun","doi":"10.1016/j.trim.2024.102169","DOIUrl":"10.1016/j.trim.2024.102169","url":null,"abstract":"<div><h3>Introduction</h3><div>Tacrolimus-induced thrombotic microangiopathy (TMA) causing acute kidney injury (AKI) without systemic features is a rare entity, particularly after non-renal solid organ transplantation.</div></div><div><h3>Case report</h3><div>We describe the case of a patient with AKI after combined heart and lung transplantation. Renal biopsy revealed acute thrombotic microangiopathy which ultimately prompted initiation of eculizumab, a monoclonal antibody targeted against complement C5, with subsequent recovery in renal function.</div></div><div><h3>Results/conclusion</h3><div>This case highlights renal isolated drug-induced TMA as a rarely reported cause of AKI post heart-lung transplantation. We emphasize the importance of performing a renal biopsy in guiding management strategies.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102169"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898542","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 class I supertypes and HLA class I alleles influence the outcome after allogeneic hematopoietic stem cell transplant from unrelated matched donor","authors":"Zorana Grubic ,&nbsp;Marija Burek Kamenaric ,&nbsp;Marija Maskalan ,&nbsp;Lana Desnica ,&nbsp;Mirta Mikulic ,&nbsp;Katarina Stingl Jankovic ,&nbsp;Nadira Durakovic ,&nbsp;Radovan Vrhovac ,&nbsp;Ranka Serventi Seiwerth ,&nbsp;Renata Zunec","doi":"10.1016/j.trim.2024.102167","DOIUrl":"10.1016/j.trim.2024.102167","url":null,"abstract":"<div><div>This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (<em>N</em> = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM.</div><div>The analysis of the subgroup of patients with AML or MDS (<em>N</em> = 148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLA-B27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM.</div><div>The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102167"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882811","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":"High seroprevalence of CMV among Algerian hemodialysis patients and the general population: Intermediate-risk patients for post-transplant CMV infection","authors":"Lydia Lamara Mahammed ,&nbsp;Zineb Omrani ,&nbsp;Nourhene Bellachia ,&nbsp;Lilya Meriem Berkani ,&nbsp;Messaoud Saidani ,&nbsp;Reda Djidjik","doi":"10.1016/j.trim.2024.102168","DOIUrl":"10.1016/j.trim.2024.102168","url":null,"abstract":"<div><h3>Introduction</h3><div>Cytomegalovirus (CMV) is a virus of the herpesviridae family. CMV infection is associated with increased morbidity and mortality in immunocompromised subjects such as hemodialysis patients and transplant recipients. The aim of our study was to determine the serological status of potential kidney recipients and donors in order to assess the risk of post-transplant CMV infection and disease.</div></div><div><h3>Patients and methods</h3><div>We included 135 and 200 potential kidney transplant donors and recipients, respectively, who were tested for anti-CMV IgM and IgG by chemiluminescence on IMMULITE 2000 XPI®.</div></div><div><h3>Results</h3><div>The prevalence of anti-CMV IgG was 95.50 % (95 % CI [92.63 %–98.37 %]) in hemodialysis patients and 96.30 % (95 % CI [93.12 %–99.48 %]) in potential kidney donors. The difference between the two groups was not significant (<em>p</em> = 0.721). Anti-CMV IgM were only detected in the sera of 13 hemodialysis patients and 3 healthy subjects. In both groups, the highest rate of anti-CMV IgG positivity was observed in subjects aged over 50 years (100 %), followed by those aged between 18 and 30 years old, with a slightly higher seroprevalence in men than in women.</div></div><div><h3>Conclusion</h3><div>Our results suggest a high prevalence of anti-CMV IgG in potential kidney donors and recipients (D+/R+), who could be classified as an intermediate risk group for post-transplant CMV infection and/or disease.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102168"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882882","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":"Prevalence of anti-HLA antibodies among live related renal transplant recipients: A retrospective observational study from a tertiary healthcare Center in India","authors":"Prashant Pandey ,&nbsp;Amit Pande ,&nbsp;Arghyadeep Marik ,&nbsp;Amit Kumar Devra ,&nbsp;Vijay Kumar Sinha ,&nbsp;Anil Prasad Bhatt ,&nbsp;Divya Setya ,&nbsp;Smriti Mishra ,&nbsp;Shantanu Jha","doi":"10.1016/j.trim.2024.102164","DOIUrl":"10.1016/j.trim.2024.102164","url":null,"abstract":"<div><h3>Aim</h3><div>Detection of anti-HLA antibodies is crucial for pre-transplant histocompatibility testing, donor selection, and graft survival. The aim of this study was to evaluate the spectrum of anti-HLA antibodies among live related renal transplant recipients from one of the largest transplant centers in north India.</div></div><div><h3>Methods</h3><div>In this study, retrospective data of transplant workup done in past four years were analyzed using GraphPad Prism 9 Version 9.2.0 (La Jolla, CA, USA). All samples received for pre-transplant work-up if showed positive screening results underwent Luminex single antigen bead (L-SAB) assay. Antibodies identified on L-SAB were evaluated for their specificity and the strength of their mean florescence intensity (MFI).</div></div><div><h3>Results</h3><div>A total of 1250 renal transplant samples were included for analysis. Out of these, 458 (36.64 %) samples were found positive in screening tests algorithm. All 458 samples were further analyzed for both class I and class II HLA antibodies by Luminex single antigen bead (L-SAB) assay. In this study, we observed that anti-A*24:01, anti-B*15:01 and anti-C*07*01 were the three most prevalent anti-HLA antibodies identified against HLA-class I antigens. However, anti-DRB1*11:01, anti-DQA1*05:01-DQB1*03:01 and anti-DPA1*02:01-DPB1*17:01 were the most common anti-HLA antibodies identified against HLA-class II antigen. Furthermore, our study found a significant association between anti-HLA class I antibody and the history of pregnancy. However, in re-transplant cases, we observed the presence of antibodies both against HLA class I and II antigens.</div></div><div><h3>Conclusion</h3><div>For a transplant center, it is of utmost importance to have comprehensive knowledge about the prevalence of HLA antibodies, their MFI, and their association with various sensitization events. This study may immensely help transplant communities in selecting appropriate prospective organ donors, planning desensitization regimes, managing recipients' care and predicting transplant outcomes in live related renal transplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102164"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882857","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":"CMV management of patients with leukopenia after CMV high-risk kidney transplantation","authors":"Amina Abu-Omar ,&nbsp;Janine Mihm ,&nbsp;Saskia Bronder ,&nbsp;Tina Schmidt ,&nbsp;Martina Sester ,&nbsp;Urban Sester","doi":"10.1016/j.trim.2025.102188","DOIUrl":"10.1016/j.trim.2025.102188","url":null,"abstract":"<div><h3>Background</h3><div>For CMV high-risk constellations, guidelines recommend 3–6 months of prophylaxis with valganciclovir (VGCV). Management in preventing CMV primary infection in patients developing VGCV-associated leukopenia remains challenging.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the development of leukopenia during VGCV prophylaxis in 57 seronegative kidney recipients of a CMV-seropositive donor between 2008 and 2021. We analyzed CMV risk and development of CMV-specific T cells in the first post-transplant year depending on leukopenia during VGCV prophylaxis and management with CMV-IVIg.</div></div><div><h3>Results</h3><div>Leukopenia developed in 19/57 patients, with a significant difference in leukocyte counts occurring after 10 weeks of VGCV prophylaxis compared to patients without leukopenia (<em>p</em> = 0.0003). VGCV discontinuation led to leukocyte reconstitution, which tended to be faster in patients receiving additional prophylaxis with CMV-IVIg after VGCV discontinuation (<em>n</em> = 11, <em>p</em> = 0.083). In the first post-transplant year, patients with leukopenia had no higher risk for severe CMV events. Interestingly, patients receiving CMV-IVIg prophylaxis showed a significantly lower peak CMV-load during primary infection (<em>p</em> = 0.040), with no difference in CMV-specific T-cell levels compared to patients without leukopenia or patients with additional CMV-IVIg prophylaxis (<em>p</em> = 0.972). Patients developing adequate CMV-specific T-cell responses less frequently underwent CMV reactivation 50 days following primary infection.</div></div><div><h3>Conclusion</h3><div>Leukopenia developed late during VGCV prophylaxis and did not result in an increased risk for CMV primary infections or severe disease. Leukopenic patients receiving CMV-IVIg tended to have a faster leukocyte reconstitution and had lower peak DNAemia, which did not adversely affect CMV-specific T-cell induction. CMV-IVIg may therefore be considered as an alternative prophylactic strategy in patients with VGCV-associated leukopenia.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102188"},"PeriodicalIF":1.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis gene characterizes the immune microenvironment of diabetic nephropathy","authors":"Liping Guo ,&nbsp;Fei Liu ,&nbsp;Hui Li ,&nbsp;Yingying Yuan ,&nbsp;Fan Lu","doi":"10.1016/j.trim.2025.102175","DOIUrl":"10.1016/j.trim.2025.102175","url":null,"abstract":"<div><h3>Background</h3><div>The cuproptosis is an intracellular copper (Cu) accumulation triggering the aggregation of mitochondrial lipoylated proteins and destabilization of iron‑sulfur (Fe<img>S) cluster proteins, leading to cell death. This copper-triggered modality of mitochondrial cell death has been associated with cuproptosis-related signature key genes (CRGs). Our study focused on the relationship between the cuproptosis CRGs and diabetic nephropathy (DN) to understand how such immune microenvironment may influence DN.</div></div><div><h3>Methods</h3><div>We downloaded and compared RNA sequencing data sets of DN glomerular tissue samples vs. normal renal tissue samples (GSE142025, GSE30528, and GSE96804) from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between DN and control samples were screened. Immune cell subtypes infiltration and immune score were figured out via different algorithms. Consensus clustering was performed by the Ward's method to determine different phenotypes of DN. CRG key genes between two phenotypes were identified via machine learning algorithm. Logistic regression analysis was applied to establish a nomogram for assessing the risk of DN.</div></div><div><h3>Results</h3><div>In DN samples, two genes NLRP3 and CDKN2A were positively correlated to the immune score. In contrast, six genes NFE2L2, LIAS, LIPT1, DLD, DBT and DLST were negatively correlated to the immune score. Via Consensus clustering based on cuproptosis CRG key genes, the DN samples were divided into cluster C1 and cluster C2. The cluster C1 was characterized by low cuproptosis CRG genes expression, high immune cell subtypes infiltration, and high enrichment of immune-related pathways. Cluster C2 was on the contrary, the Dicarbonyl/l-xylulose reductase (DCXR) and heat-responsive protein 12 (HRSP12) genes were related to clinical traits and the immune microenvironment, negatively correlated with most immune cell subtypes. The nomogram was constructed based on DCXR and HRSP12 showing good efficiency for the DN diagnosis.</div></div><div><h3>Conclusion</h3><div>We conclude that the immune microenvironment imbalance and metabolic disorders lead to the occurrence of DN. The signature cuproptosis genes, regulating the immune microenvironment and metabolism, represented the DN disease clustering to describe the heterogeneity and characterize immune microenvironment. Both HRSP12 and DCXR key genes are related to DN disease phenotypes and immune microenvironment characteristic and may help in DN diagnosis.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102175"},"PeriodicalIF":1.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075588","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 reconstitution with high-dose chemotherapy and autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Prognostic factors and outcome from a single-center experience","authors":"Fawaz S. Yousif ,&nbsp;Bassam Francis Matti ,&nbsp;Shahla'a Fadhil Sabir ,&nbsp;Zena A. AL-Bakri ,&nbsp;Safa A. Faraj ,&nbsp;Mazin A. Mohammed ,&nbsp;Zahraa S. Shakir ,&nbsp;Mahmood W. Khalid ,&nbsp;Saba H. Al Hlali ,&nbsp;Sarah M. Saeb","doi":"10.1016/j.trim.2025.102182","DOIUrl":"10.1016/j.trim.2025.102182","url":null,"abstract":"<div><h3>Background</h3><div>Autologous stem cell transplantation (ASCT) imposes significant immunogenic effects that may also underlie some of its anti-tumor effectiveness. Despite improvements in disease risk stratification and treatment approaches with high cure and response rate for newly diagnosed Hodgkin lymphoma (HL) with initial therapy in most patients, a significant proportion will be experiencing refractory or relapsed (R/R) following the initial front-line therapy. A high-dose chemotherapy followed by ASCT remains the standard treatment for relapsed Hodgkin disease in adult patients. The aim of our study was to identify the impact of ASCT on outcomes in R/R HL, considering various pre- and post-ASCT parameters as prognostic predictors, including disease status response, time of absolute neutrophils, and lymphocyte recovery counts post ASCT.</div></div><div><h3>Methods</h3><div>We retrospectively investigated data of 118 patients with R/RHL from January 2014 to December 2022, whose ages ranged from 7 to 58 years old. The recorded data included: the early response type and mortality rate, at day 100 post-ASCT, as well as the end of the study outcomes such as survival, relapse, and mortality status. Patients were grouped according to gender, disease status pre-ASCT, number of chemotherapy protocols that were given pre-ASCT, time of absolute neutrophils and lymphocyte recovery counts post-ASCT.</div></div><div><h3>Results</h3><div>The mean age of our included patients was 25.1 (7–58) years. The male to female ratio was1.2:1with a mean duration of disease follow-up was 74.2 months. The mean duration time of absolute neutrophil and lymphocyte recovery count post-ASCT day was 11 ± 2.9 and 13 ± 2.6 days respectively. The outcome at 100 days post-ASCT was: 89.8 % of the patients showed complete remission, 6.8 % showed no response, and 3.4 % deceased. The three-year overall survival (OS) rate was 88.5 %, while the event free survival (EFS) rate was 72 %. Regarding the three-year EFS rate for patient with complete remission was 91 %, for patients with uncertain complete response was 71 %, also 71 % for partial remission and 45 % for stable disease. The EFS rate in relation to the number of chemotherapy protocols at three-year follow up was 80 % and 66 % for patients with ≥2 chemotherapy lines(<em>P</em> = 0.03).</div></div><div><h3>Conclusion</h3><div>Autologous stem cell transplantation for R/R HL patients demonstrated a significant favorable outcome in terms of the overall survival rate and the progression-free disease, especially among those who exhibited earlier response to salvage chemotherapy at the pre-transplantation stage and unrelated to time of absolute neutrophil and lymphocyte recovery count.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102182"},"PeriodicalIF":1.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075609","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":"Trametinib alleviates lipopolysaccharide-induced acute kidney injury by inhibiting macrophage polarization through the PI3K/Akt pathway","authors":"Yingqi Zeng ,&nbsp;Wenjia Yuan ,&nbsp;Chen Feng ,&nbsp;Longkai Peng ,&nbsp;Xubiao Xie ,&nbsp;Fenghua Peng ,&nbsp;Tengfang Li ,&nbsp;Minjie Lin ,&nbsp;Hedong Zhang ,&nbsp;Helong Dai","doi":"10.1016/j.trim.2025.102183","DOIUrl":"10.1016/j.trim.2025.102183","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced acute kidney injury (AKI) is a severe condition characterized by dysregulation of pro- and anti-inflammatory responses. Targeting macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 cells offers a potential therapeutic approach for AKI. Trametinib (TRAM), an inhibitor of the MEK1/2 signaling pathway, was evaluated for its impact on M1/M2 polarization in AKI.</div></div><div><h3>Methods</h3><div>Wild-type (WT) mice were subjected to lipopolysaccharide (LPS)-induced AKI and intraperitoneally treated with dimethyl sulfoxide (DMSO) or TRAM (10 mg/kg) for three days. Renal function was assessed by measuring creatinine levels. While histopathological changes, RNA sequencing data, and serum cytokine levels were analyzed. Macrophage M1/M2 polarization in kidney tissues was examined using flow cytometry and immunohistochemistry. Murine bone marrow-derived macrophages (BMDMs) were polarized to the M1 or M2 phenotype in vivo and treated with or without TRAM (10 μM). M1/M2 polarization was analyzed via flow cytometry, and PI3K/Akt signaling was evaluated by western blotting.</div></div><div><h3>Results</h3><div>TRAM significantly improved renal function, as demonstrated by reduced serum creatinine levels (<em>p</em> &lt; 0.01) and ameliorated histopathological damage (p &lt; 0.01). Flow cytometry and immunohistochemistry revealed that TRAM markedly inhibited pro-inflammatory M1 macrophage polarization (<em>p</em> &lt; 0.001). Additionally, TRAM reduced serum level of IFN-γ (<em>p</em> &lt; 0.01) and IL-17 (p &lt; 0.001). In vitro, TRAM suppressed M1 polarization (<em>p</em> &lt; 0.05) by inhibiting the PI3K/Akt signaling pathway.</div></div><div><h3>Conclusion</h3><div>TRAM mitigated LPS-induced AKI by suppressing M1 macrophage polarization via the PI3K/Akt pathway, highlighting its therapeutic potential for AKI and other inflammatory kidney diseases.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102183"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075556","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}