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MHC Class II Sharing Appears to Promote Intestinal Allograft Tolerance Through Linked Suppression in a Large Animal Model. 在大型动物模型中,MHC II类共享似乎通过关联抑制促进肠道同种异体移植物耐受性。
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-05-20 DOI: 10.1097/TP.0000000000005420
M Esad Gunes, Satyajit Patwardhan, Sarah Merl, Kryscilla Yang, Rebecca Jones, Bryan Chen, Elin Manell, Julie Hong, Philip Jordache, Hussein Atta, Ishit Chauhan, Ahmed Almesallmy, Abrar Shamim, Obinna Agwuncha, Harko Mulder, Amarnath Dasari, Dominik Hajosi, Robert J Hawley, Greg Nowak, Marcus Pereira, Huaibin Mabel Ko, Dilrukshi Ekanayake-Alper, Mercedes Martinez, David H Sachs, Tomoaki Kato, Kazuhiko Yamada, Megan Sykes, Joshua Weiner
{"title":"MHC Class II Sharing Appears to Promote Intestinal Allograft Tolerance Through Linked Suppression in a Large Animal Model.","authors":"M Esad Gunes, Satyajit Patwardhan, Sarah Merl, Kryscilla Yang, Rebecca Jones, Bryan Chen, Elin Manell, Julie Hong, Philip Jordache, Hussein Atta, Ishit Chauhan, Ahmed Almesallmy, Abrar Shamim, Obinna Agwuncha, Harko Mulder, Amarnath Dasari, Dominik Hajosi, Robert J Hawley, Greg Nowak, Marcus Pereira, Huaibin Mabel Ko, Dilrukshi Ekanayake-Alper, Mercedes Martinez, David H Sachs, Tomoaki Kato, Kazuhiko Yamada, Megan Sykes, Joshua Weiner","doi":"10.1097/TP.0000000000005420","DOIUrl":"https://doi.org/10.1097/TP.0000000000005420","url":null,"abstract":"<p><strong>Background: </strong>The relative importance of major histocompatibility complex (MHC) class I and class II matching for the induction of transplantation tolerance remains unclear. We studied selective mismatches in a clinically relevant model of intestinal transplantation (ITx) in swine with defined MHC genotypes.</p><p><strong>Methods: </strong>We performed orthotopic ITx between MHC haplotype-matched (n = 6), partially matched (having class II alleles with marked overlap, n = 2), and fully mismatched (n = 4) pairs. Immunosuppression mirrored our clinical protocol and was weaned off between days 90 and 140.</p><p><strong>Results: </strong>The fully mismatched animals did not develop evidence of tolerance. In contrast, the partially matched animals developed a previously undefined form of \"split tolerance\" characterized by local graft tolerance mediated by donor regulatory T cells (Treg). In haplotype-matched animals, which share 1 full class II allele, Treg were also detectable in the periphery, where they appeared to promote donor-specific hyporesponsiveness and durable mixed chimerism. In vitro analyses, including a novel mucosal mixed lymphocyte reaction assay, suggested that the mechanism by which class II sharing promotes Treg-mediated tolerance is via linked suppression to allele combinations coexpressed on the same antigen-presenting cell in vivo.</p><p><strong>Conclusions: </strong>Because humans often share some class II antigenic specificities that can be determined by tissue typing pretransplant, these findings may have important implications for the induction of clinical tolerance to ITx.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":"109 9","pages":"1506-1519"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence and Outcomes of Diaphragmatic Hernia After Living Donor Hepatectomy: The Significance of Bipolar Irrigated Sealer Use. 活体肝切除术后膈疝的发生率和预后:双极灌洗封口器使用的意义。
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-03-10 DOI: 10.1097/TP.0000000000005362
Sang-Hoon Kim, Sung-Gyu Lee, Shin Hwang, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tea-Yong Ha, Gi-Won Song, Gil-Chun Park, Young-In Yoon, Ji Hoon Kim, Woo-Hyoung Kang, Eun-Kyoung Jwa, Byeong-Gon Na, Sung Min Kim, Rak-Kyun Oh, I-Ji Jeong, Hyo Jung Ko, Minha Choi, Dae Hyeon Won, Do Young Lee, Ji Hoon Kang, Dong-Hwan Jung
{"title":"Incidence and Outcomes of Diaphragmatic Hernia After Living Donor Hepatectomy: The Significance of Bipolar Irrigated Sealer Use.","authors":"Sang-Hoon Kim, Sung-Gyu Lee, Shin Hwang, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tea-Yong Ha, Gi-Won Song, Gil-Chun Park, Young-In Yoon, Ji Hoon Kim, Woo-Hyoung Kang, Eun-Kyoung Jwa, Byeong-Gon Na, Sung Min Kim, Rak-Kyun Oh, I-Ji Jeong, Hyo Jung Ko, Minha Choi, Dae Hyeon Won, Do Young Lee, Ji Hoon Kang, Dong-Hwan Jung","doi":"10.1097/TP.0000000000005362","DOIUrl":"10.1097/TP.0000000000005362","url":null,"abstract":"<p><strong>Background: </strong>Acquired diaphragmatic hernia (DH) is a rare and potentially fatal complication after living donor hepatectomy (LDH). This study aimed to assess the incidence and clinical outcomes of DH after LDH.</p><p><strong>Methods: </strong>Four thousand fourteen living donors who underwent LDH at Asan Medical Center, Seoul, between September 2013 and August 2023 were retrospectively reviewed. We analyzed the incidence of DH before and after the introduction of the bipolar irrigated sealer (BIS). Multivariate logistic regression analysis was used to identify the risk factors for DH.</p><p><strong>Results: </strong>Postoperative DH occurred in 18 patients (0.40%). Seventeen patients underwent right LDH and developed right-sided DH, whereas 1 patient underwent left LDH and developed left-sided DH. The incidence of DH was 0.22% in the pre-BIS period and >6-fold to 1.36% in the post-BIS period. The median time of postoperative DH occurrence was 11 (range, 3-95) mo. Ten patients underwent elective surgery for DH repair, whereas 8 patients with severe abdominal pain or bowel obstruction underwent emergency surgery, 1 of whom underwent small bowel resection and anastomosis due to severe bowel incarceration. Using BIS was the only significant risk factor for developing DH ( p  < 0.001; odd ratio, 6.28; 95% confidence interval, 2.43-16.25).</p><p><strong>Conclusions: </strong>Early recognition and surgical repair of DH after LDH should be considered in living donors with unexplained abdominal or thoracic symptoms. Caution is advised when using peridiaphragmatic hemostasis with BIS in liver surgery. We recommend extending the postoperative follow-up of living donors to at least 3 y, including routine imaging screenings for DH.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e494-e500"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy. 供体变异和PD-1表达限制BK多瘤病毒特异性t细胞功能和治疗
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-04-09 DOI: 10.1097/TP.0000000000005399
Maud Wilhelm, Amandeep Kaur, Anne Geng, Marion Wernli, Hans H Hirsch
{"title":"Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.","authors":"Maud Wilhelm, Amandeep Kaur, Anne Geng, Marion Wernli, Hans H Hirsch","doi":"10.1097/TP.0000000000005399","DOIUrl":"10.1097/TP.0000000000005399","url":null,"abstract":"<p><strong>Background: </strong>BK polyomavirus (BKPyV) nephropathy is a major cause of premature kidney transplant failure. Current management relies on reducing immunosuppression to restore BKPyV-specific immune control. Ex vivo expansion and transfer of BKPyV-specific cytotoxic T cells prepared from third-party donors may enhance virus-specific treatment, but the efficacy seems suboptimal.</p><p><strong>Methods: </strong>To optimize BKPyV-specific T-cell expansion protocols, we compared conventional and G-Rex expansion cultures at 10 and 14 d after stimulation with BKPyV overlapping peptide pools. Cytokine and cytotoxic responses were assessed as well as programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-1L) expression on effector and target cells, respectively.</p><p><strong>Results: </strong>Despite all donors being BKPyV-IgG seropositive, BKPyV-specific T-cell responses were heterogeneous and varied in magnitude between individuals. Overall, we observed higher cell counts in G-Rex compared to conventional cultures. Upon restimulation with 15mer-pools or immunodominant 9mer-pools, expanded BKPyV-specific T cells expressed polyfunctional markers, for example, interferon-γ, tumor necrosis factor-α and CD107a, and were cytotoxic for 9mP-pulsed autologous phytohemagglutinin blasts or BKPyV-infected allogeneic renal proximal tubule epithelial cells (RPTECs). Compared with conventional cultures, G-Rex-expanded CD4 and CD8 T cells showed higher PD-1 expression. Pembrolizumab reduced PD-1 expression on BKPyV-specific T cells and augmented polyfunctional BKPyV-specific T-cell responses and cytotoxicity. Interferon-𝛾 increased PD-L1 expression on BKPyV-infected RPTECs and increased viability.</p><p><strong>Conclusions: </strong>Upregulated PD-1 expression of ex vivo expanded T cells contributes to third-party donor variability and potentially impairs the efficacy of adoptive T-cell therapy. Because BKPyV-infected RPTECs increase PD-L1 under inflammatory conditions, adding immune checkpoint inhibitors ex vivo before infusion could be evaluated for enhanced clinical efficacy when attempting treatment of BKPyV-associated pathologies without jeopardizing transplantation outcomes.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1526-1539"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients. 胰高血糖素样肽-1受体激动剂对肝移植受者代谢健康的影响
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-03-25 DOI: 10.1097/TP.0000000000005361
Idris Yakubu, Joseph Spengler, Perry Taylor, Michael LaPorte, Andrew Brown, Sara Sterling, Bem Agegnehu, Aoife Iaria, Ryan Marks, Taylor Sprague, Vasco Pontinha, Vaishali Patel, Kavish R Patidar, Mohammad Shadab Siddiqui
{"title":"Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients.","authors":"Idris Yakubu, Joseph Spengler, Perry Taylor, Michael LaPorte, Andrew Brown, Sara Sterling, Bem Agegnehu, Aoife Iaria, Ryan Marks, Taylor Sprague, Vasco Pontinha, Vaishali Patel, Kavish R Patidar, Mohammad Shadab Siddiqui","doi":"10.1097/TP.0000000000005361","DOIUrl":"10.1097/TP.0000000000005361","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), initially approved for the management of diabetes, have demonstrated a wide range of metabolic benefits. However, their benefit and safety profile in liver transplant (LT) recipients remain poorly defined.</p><p><strong>Methods: </strong>This study retrospectively analyzed adults who had undergone LT and had concomitant type 2 diabetes mellitus. Thirty-eight post-LT recipients treated with GLP-1RA for type 2 diabetes mellitus were matched with patients treated with insulin therapy 1:1 using propensity scoring for age, sex, ethnicity, cause of cirrhosis, and immunosuppression. This matching aimed to assess the metabolic effects and safety profile of GLP-1RA after LT.</p><p><strong>Results: </strong>The 2 groups were similar at baseline with regard to clinical characteristics, except that time from LT was greater in patients who were on GLP-1RA. Semaglutide was the most commonly used GLP-1RA. LT recipients who received GLP-1RA lost approximately 8% of body weight during 12 mo, whereas patients on insulin therapy gained approximately 10% of body weight during the same period. Patients on GLP-1RA were less likely to have hepatic steatosis compared with patients on insulin therapy post-LT. Both GLP-1 and insulin were well tolerated, with no significant impact on renal function, immunosuppression, or rejection. GLP-1RA was stopped in only 1 patient due to persistent nausea.</p><p><strong>Conclusions: </strong>GLP-1RA therapy is safe after LT and is well tolerated. Aside from glycemic control, metabolic benefits of GLP-1RA included weight loss and lower prevalence of steatosis in LT recipients. The study findings provide much-needed safety data for GLP-1RA in LT patients and foundational data to design prospective trials to evaluate metabolic benefits of GLP-1RA.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e501-e507"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HLA-EP-RESOLVER: A Novel Web-based Bioinformatic Tool to Determine the Presence or Absence of DSA Against Rare HLA Alleles in the Era of Rapid High-resolution Deceased Donor HLA Genotyping. HLA- ep - resolver:在快速高分辨率已故供者HLA基因分型时代,一种新的基于网络的生物信息学工具,用于确定针对罕见HLA等位基因的DSA是否存在。
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-04-21 DOI: 10.1097/TP.0000000000005404
Linh Truong, Fredrick Mobegi, Babette Vogels, Dianne De Santis, Jonathan Downing, Lloyd D'Orsogna
{"title":"HLA-EP-RESOLVER: A Novel Web-based Bioinformatic Tool to Determine the Presence or Absence of DSA Against Rare HLA Alleles in the Era of Rapid High-resolution Deceased Donor HLA Genotyping.","authors":"Linh Truong, Fredrick Mobegi, Babette Vogels, Dianne De Santis, Jonathan Downing, Lloyd D'Orsogna","doi":"10.1097/TP.0000000000005404","DOIUrl":"10.1097/TP.0000000000005404","url":null,"abstract":"<p><strong>Background: </strong>Patients awaiting a solid organ transplant require pretransplant testing including high-resolution HLA typing and screening of HLA antibodies. However, the standard HLA antibody testing cannot encompass all the HLA alleles available in the Australian donor pool. With the advent of high-resolution HLA typing for organ allocation, there is an increased prevalence of detecting uncommon HLA alleles. It is challenging to manually determine whether patients have donor-specific HLA antibodies against these antigens. To address this issue, a bioinformatic pipeline, HLA-EP-RESOLVER, was developed to assess eplet reactivity for rare HLA unacceptable antigens (UAs).</p><p><strong>Methods: </strong>The HLA-EP-RESOLVER pipeline was validated against sensitized patients, and a list of candidate UAs was identified for each patient. The candidate UAs must meet the following criteria: (1) match at the first field with existing UAs, (2) share eplets or serological types with the current UAs, (3) do not share the patient's self-eplets or eplets on negative beads, and/or (4) in the exception rules. The Australian deceased donor pool was used as the initial model. The predicted UAs were then confirmed with physical crossmatching.</p><p><strong>Results: </strong>The pipeline proved to be highly accurate at predicting high-risk antigens by utilizing eplet analysis through HLA Matchmaker, and the HLA data extracted from the Australian donor population. The reactivity of several candidate UAs were confirmed by cellular verification.</p><p><strong>Conclusions: </strong>The HLA-EP-RESOLVER program was shown to be rapid, useful, and highly accurate in determining acceptable or unacceptable HLA alleles in the new era of rapid high-resolution donor typing before allocation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e508-e525"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating Tissue Specific Extracellular Vesicles for Noninvasive Monitoring of Acute Cellular Rejection in Clinical Heart Transplantation. 循环组织特异性细胞外囊泡无创监测临床心脏移植急性细胞排斥反应。
IF 5 2区 医学
Transplantation Pub Date : 2025-09-01 Epub Date: 2025-04-16 DOI: 10.1097/TP.0000000000005369
Laxminarayana Korutla, Robert Hu, Yihan Liu, Connie Romano, Andreas Habertheuer, Parisa Abedi, He Wang, Sudheer Molugu, Susan Rostami, Ali Naji, Abdulelah Nuqali, Michael Beasley, Christopher Maulion, Samuel Hahn, Tariq Ahmad, Zuoheng Wang, Sounok Sen, Prashanth Vallabhajosyula
{"title":"Circulating Tissue Specific Extracellular Vesicles for Noninvasive Monitoring of Acute Cellular Rejection in Clinical Heart Transplantation.","authors":"Laxminarayana Korutla, Robert Hu, Yihan Liu, Connie Romano, Andreas Habertheuer, Parisa Abedi, He Wang, Sudheer Molugu, Susan Rostami, Ali Naji, Abdulelah Nuqali, Michael Beasley, Christopher Maulion, Samuel Hahn, Tariq Ahmad, Zuoheng Wang, Sounok Sen, Prashanth Vallabhajosyula","doi":"10.1097/TP.0000000000005369","DOIUrl":"10.1097/TP.0000000000005369","url":null,"abstract":"<p><strong>Background: </strong>There remains a critical need for biomarkers of acute cellular rejection (ACR) in heart transplantation. We hypothesized that immunopathophysiology of ACR is reflected via dynamic changes in the protein and RNA cargoes of small extracellular vesicles (sEVs) released by cardiac allograft and T cells into circulation, thus enabling noninvasive window into ACR.</p><p><strong>Methods: </strong>T-cell sEVs were enriched using anti-CD3 antibody beads, and antidonor HLA I antibody beads for donor sEVs. Cargoes of donor sEVs (cardiac troponin T [cTnT] protein and mRNA) and T-cell sEVs (CD4, CD8, T-cell receptor proteins, miRNAs [miRs] let 7i, 101b, 21a) were compared with time-matched endomyocardial biopsy samples (n = 70) in 12 patients to postoperative day 120.</p><p><strong>Results: </strong>Six patients had 11 moderate ACR (15.7%) episodes, 1 had antibody-mediated rejection, and 5 had ≤ mild ACR. By Wilcoxon rank-sum tests, cTnT protein ( P  = 6.04 × 10 -5 ) and mRNA ( P  = 6.87 × 10 -7 ) were decreased with moderate ACR compared with grades 0/1 ACR. T-cell sEV CD4, CD8, and TCR protein cargoes ( P ≤ 3.92 × 10 -5 ) and miRs let 7i, 101b, and 21a ( P ≤ 9.05 × 10 -5 ) were increased with moderate ACR. Successful treatment of moderate ACR led to dynamic reversal in sEV profiles, especially donor heart sEV cTnT mRNA (Spearman coefficient 0.87) and miR 21a (coefficient 0.85).</p><p><strong>Conclusions: </strong>Our first investigation in heart transplant patients demonstrated that circulating T cell-sEV and donor heart-sEV profiles enable diagnosis of moderate ACR with high diagnostic accuracy. A large sample cohort external validation study is warranted to better understand diagnostic potential of this platform for ACR monitoring in heart transplantation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1540-1550"},"PeriodicalIF":5.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predicting Cytomegalovirus Infection in Seropositive Lung Transplant Recipients: How to Improve the Predictive Performance? 预测血清阳性肺移植受者巨细胞病毒感染:如何提高预测效果?
IF 5 2区 医学
Transplantation Pub Date : 2025-08-29 DOI: 10.1097/TP.0000000000005517
Zhi-Qiang Deng, Hao-Ji Yan, Dong Tian
{"title":"Predicting Cytomegalovirus Infection in Seropositive Lung Transplant Recipients: How to Improve the Predictive Performance?","authors":"Zhi-Qiang Deng, Hao-Ji Yan, Dong Tian","doi":"10.1097/TP.0000000000005517","DOIUrl":"https://doi.org/10.1097/TP.0000000000005517","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-CTLA-4 Treatment Abrogates Co-stimulation Blockade-induced Acceptance of Transgenic Porcine Islets in Humanized Mice. 抗ctla -4治疗可消除共刺激阻断诱导的人源化小鼠对转基因猪岛的接受。
IF 5 2区 医学
Transplantation Pub Date : 2025-08-26 DOI: 10.1097/TP.0000000000005512
Jochen Seissler, Constanca Figueiredo, Elisabeth Kemter, Nikolai Klymiuk, Eckhard Wolf, Lelia Wolf-van Buerck
{"title":"Anti-CTLA-4 Treatment Abrogates Co-stimulation Blockade-induced Acceptance of Transgenic Porcine Islets in Humanized Mice.","authors":"Jochen Seissler, Constanca Figueiredo, Elisabeth Kemter, Nikolai Klymiuk, Eckhard Wolf, Lelia Wolf-van Buerck","doi":"10.1097/TP.0000000000005512","DOIUrl":"https://doi.org/10.1097/TP.0000000000005512","url":null,"abstract":"<p><strong>Background: </strong>In previous studies, we showed that beta cell-specific overexpression of high-affinity variant of human CTLA-4 (LEA29Y), a high-affinity variant of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)-immunoglobulin, prevented porcine islet rejection in humanized mouse models. We here investigate whether long-term xenograft function and survival is maintained after neutralization of LEA29Y-mediated co-stimulation blockade.</p><p><strong>Methods: </strong>Diabetic humanized NOD-SCID IL2rγ-/- mice were transplanted with transgenic neonatal porcine islet-like clusters expressing LEA29Y under control of the porcine insulin promoter. After development of normal glucose tolerance, mice were treated with blocking anti-CTLA-4 antibody (Ab) or isotype control Ab. Reoccurrence of diabetes, plasma cytokines/chemokines and graft histology were analyzed.</p><p><strong>Results: </strong>Systemic treatment with an inhibitory anti-humanized CTLA-4 Ab led to a significant increase of pro-inflammatory plasma cytokine production (interferon gamma, monokine induced by interferon gamma; P < 0.05) at day 14 and reoccurrence of diabetes in 100% of the animals within 40 d after Ab application (P = 0.01). Strong infiltration with human CD45+ cells consisting mainly of CD4+ and CD8+ T cells and some B lymphocytes and few destructed remaining beta cells were observed in the treatment group indicating rapid and severe graft rejection.</p><p><strong>Conclusions: </strong>The present data demonstrate that long-lasting acceptance of LEA29Y transgenic porcine islet grafts is dependent on CTLA-4/LEA29Y signaling even several months after transplantation. This finding has important implications on safety of pig islet xenotransplantation in patients with type 1 diabetes because it provides a potent tool for graft elimination in case of medical indication.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evolving Ethical Challenges After a Decade of Uterus Transplantation: Recommendations From the International Society of Uterus Transplantation Ethics Committee. 子宫移植十年后不断演变的伦理挑战:来自国际子宫移植伦理委员会的建议。
IF 5 2区 医学
Transplantation Pub Date : 2025-08-26 DOI: 10.1097/TP.0000000000005507
Anji E Wall, Mats Brännström, Mianna Lotz, Catherine Racowsky, Peter Stock, Stina Järvholm, Petr Sustek, Sara Brucker, Stefan G Tullius
{"title":"Evolving Ethical Challenges After a Decade of Uterus Transplantation: Recommendations From the International Society of Uterus Transplantation Ethics Committee.","authors":"Anji E Wall, Mats Brännström, Mianna Lotz, Catherine Racowsky, Peter Stock, Stina Järvholm, Petr Sustek, Sara Brucker, Stefan G Tullius","doi":"10.1097/TP.0000000000005507","DOIUrl":"https://doi.org/10.1097/TP.0000000000005507","url":null,"abstract":"<p><p>Uterus transplantation (UTx) became a clinical reality with the birth of the first baby in 2014. Following increased success, the procedure has now transitioned to clinical practice in many institutions throughout the world. With a rising number of donors, recipients, and babies born from this procedure, and with more institutions offering UTx, ethical challenges have evolved while novel aspects gained prominence. Here, the Ethics Committees of the International Uterus Transplantation Society, a section of The Transplantation Society, summarize current and future ethical challenges in UTx and provide recommendations for addressing these challenges. Ethical considerations covered here span (i) donor and recipient selection, (ii) living versus deceased donation, (iii) use of assisted reproductive technologies, (iv) informed consent, (v) clinical provision of UTx, and (vi) research protocols for further studies of UTx. For each topic considered, ethical analysis and recommendations are offered to ensure the practice of UTx remains within an acceptable foundational ethical framework that balances respect for autonomy, beneficence, and justice.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HLA-DQA1*03:02-DQB1*03:03 is the Dominant Immunogenic Heterodimer for Posttransplant HLA-DQ De Novo DSA Development in a Cohort of Chinese Kidney Transplant Patients. HLA-DQA1*03:02-DQB1*03:03是中国肾移植患者移植后HLA-DQ De Novo DSA发展的显性免疫原性异二聚体。
IF 5 2区 医学
Transplantation Pub Date : 2025-08-26 DOI: 10.1097/TP.0000000000005445
Zhaoru Huang, Yonghua Feng, Xiangjun Liu, Xiaobo Li, Jinfeng Li, Lei Liu, Hongchang Xie, Zhigang Wang, Junxiang Wang, Yongchuang Yan, Frans H J Claas, Guiwen Feng, Wenjun Shang
{"title":"HLA-DQA1*03:02-DQB1*03:03 is the Dominant Immunogenic Heterodimer for Posttransplant HLA-DQ De Novo DSA Development in a Cohort of Chinese Kidney Transplant Patients.","authors":"Zhaoru Huang, Yonghua Feng, Xiangjun Liu, Xiaobo Li, Jinfeng Li, Lei Liu, Hongchang Xie, Zhigang Wang, Junxiang Wang, Yongchuang Yan, Frans H J Claas, Guiwen Feng, Wenjun Shang","doi":"10.1097/TP.0000000000005445","DOIUrl":"https://doi.org/10.1097/TP.0000000000005445","url":null,"abstract":"<p><strong>Background: </strong>Eplets, acting as specificity determinants on donor HLA antigen molecules, may induce the formation of de novo donor-specific antibodies (dnDSAs) by the recipient's B cells posttransplantation. HLA-DQ DSAs are the most common type of DSAs that target mismatched donor HLA-DQ antigens. The HLA-DQ protein exists as a heterodimer, consisting of HLA-DQA1 and HLA-DQB1 molecules. The specific risk of each mismatched HLA-DQ dimer contributing to dnDSA formation remains underexplored.</p><p><strong>Methods: </strong>A total of 434 kidney transplant donor/recipient pairs from Zheng Zhou University First Affiliated Hospital, who underwent the transplant procedure between September 2016 and November 2020, were included in this analysis. All were DSA-negative pretransplant. For each HLA-DQ heterodimer, the total incidence of dnDSA, alpha chain-specific dnDSA, and beta chain-specific dnDSA after kidney transplant was analyzed. The dnDSA formation rates of different mismatched HLA-DQ dimers were compared and their haplotype association with specific HLA-DRB1 protein were determined.</p><p><strong>Results: </strong>In this study, 38 HLA-DQ dnDSAs were detected, with 28 to HLA-DQB1 and 10 to HLA-DQA1. HLA-DQA1*03:02-DQB1*03:03 dimer had the highest dnDSA formation rate of 28.3%. The HLA-DQA1*05:xx-DQB1*03:01 and HLA-DQA1*05:xx-DQB1*02:xx, which are known for their high immunogenicity in previous studies, showed a relatively low DSA formation rate of 4.3%. The common DQB1*01:xx-DQB1*05:xx and DQA1*01:xx-DQB1*06:xx dimers had DSA formation rates of 1.8% and 3.9%, respectively. The high immunogenic HLA-DQA1*03:02-DQB1*03:03 dimer formed haplotype with DRB1*09:01 (98%), whereas the low immunogenic HLA-DQA1*02:01-DQB1*03:03 dimer formed exclusively haplotype with DRB1*07:01.</p><p><strong>Conclusions: </strong>The DQA1*03:02-DQB1*03:03 dimer and the HLA-DRB1*09:01-HLA-DQA1*03:02-DQB1*03:03 haplotype turned out to be the most immunogenic in inducing HLA-DQ dnDSA in this Northern Han Chinese cohort.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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