Transplantation最新文献

{"title":"Hidden Markov Models Offer a Powerful Approach for Understanding Gene Regulation Mechanisms Relevant for Organ Transplantation.","authors":"Carlos Goncalves, Marissa Di Napoli, David Schwartz, Bruce Kaplan","doi":"10.1097/TP.0000000000005419","DOIUrl":"10.1097/TP.0000000000005419","url":null,"abstract":"<p><p>The human genome contains sequences of DNA enriched in cytosine-guanine dinucleotides known as CpG islands (CGIs). CGIs play a crucial role in gene regulation and expression, making them an important target for genetic therapies. In this article, hidden Markov models (HMMs) and adaptive window techniques (AWTs) were used to identify CGIs in MUC5B and DSP genes. Both genes are associated with idiopathic pulmonary fibrosis, a progressive pulmonary disease that leads to a lung transplant. The University of California, Santa Cruz Genome Browser was used to obtain the MUC5B and DSP gene sequences and predefined CGI locations. The HMM and AWT algorithms were developed using Python version 3.11.5, and the outcomes analyzed were sensitivity, specificity, computational memory, and runtime. Both HMM and AWT exhibited high specificity; however, HMM was more accurate than AWT for both genes, 99% versus 96%, respectively. The HMM sensitivity was higher for both MUC5B and DSP genes (87% and 88%) compared with only 58% for MUC5B and 57% for DSP with AWT. Regarding computational efficiency, AWT was faster and required less memory than HMM for both genes. By accurately detecting CpG-rich regions, HMM offers a powerful approach to understanding gene regulation mechanisms. This could pave the way for more precise therapeutic interventions, enabling targeted treatment strategies for a range of genetic disorders, including idiopathic pulmonary fibrosis, improving patient outcomes, and advancing personalized medicine.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1335-1339"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476871","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}

{"title":"In Memoriam: Dr Joshua (Josh) Levitsky.","authors":"Fadi Issa","doi":"10.1097/TP.0000000000005426","DOIUrl":"https://doi.org/10.1097/TP.0000000000005426","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":"109 8","pages":"1261-1262"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708971","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}

{"title":"Tissue-based Gene Expression Diagnosis of Mild and Moderate T-cell-mediated Rejection to Guide Therapy in Kidney Transplants.","authors":"Dhiren Kumar, Nihar Raju, Bekir Tanriover, Louiza Azzouz, Irfan Moinuddin, Mary Philogene, Layla Kamal, Felecia McDougan, Hugh Davis Massey, Selvaraj Muthusamy, Inkoo Lee, Philip Halloran, Gaurav Gupta","doi":"10.1097/TP.0000000000005296","DOIUrl":"10.1097/TP.0000000000005296","url":null,"abstract":"<p><strong>Background: </strong>Mild histologic lesions of tubulo-interstitial inflammation could represent a \"response-to-wounding\" rather than allorecognition. Tissue gene expression may complement histopathology for T-cell-mediated rejection (TCMR) diagnostics.</p><p><strong>Methods: </strong>We report on the incorporation of tissue gene expression testing using a Molecular Microscope Diagnostic System into the management of kidney transplant biopsies with suspected TCMR. Patients (N = 209) were divided into 3 groups based upon diagnosis and TCMR therapy (with high-dose steroids and/or anti-thymocyte globulin): Group 1: Untreated histologic TCMR with molecular quiescence (H+M-); Group 2: Treated histologic and molecular TCMR (H+M+); and Group 3: Controls, with no histologic or molecular (H-M-) rejection.</p><p><strong>Results: </strong>At biopsy, estimated glomerular filtration rate was worse ( P = 0.006) in H+M+ (N = 35; 33 ± 22 mL/min/1.73 m 2 ) and H+M- (N = 30; 40 ± 18 mL/min/1.73 m 2 ) groups; compared with H-M- (N = 144; 47 ± 24 mL/min/1.73 m 2 ) group. In H+M- biopsies, mean molecular acute kidney injury scores (0.33 versus 0.10; P = 0.03) were higher than in H-M-; while molecular TCMR was lower compared with H+M+ (0.04 versus 0.54; P < 0.001). At 12 m postbiopsy estimated glomerular filtration rate remained low ( P < 0.001) in H+M+ (38 ± 22 mL/min/1.73 m 2 ) but improved in untreated H+M- (44 ± 22 mL/min/1.73 m 2 ) and H-M- (50 ± 23 mL/min/1.73 m 2 ) groups. At a mean follow-up of 2.1 ± 1.2 y post-index biopsy, death-censored graft survival was lower in H+M+ (74%) than in H+M- (90%) and H-M- (92%; P = 0.001). H+M+ cases had numerically higher rejection on follow-up biopsy (20%) than H+M- (7%) ( P = 0.12) and de novo donor-specific antibody formation (H+M+ 24%; H+M- 10%; P = 0.13).</p><p><strong>Conclusions: </strong>In this large single-center study, biopsies with untreated histological TCMR and molecular quiescence had comparable clinical outcomes to cases with no rejection, whereas those with histologic and tissue gene expression confirmed TCMR had inferior outcomes.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1402-1412"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878162","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}

{"title":"Generation of SLA-DQ Knockout Pigs and Screening for Anti-SLA-DQ Antibodies in Sera From Naïve and HLA Class II-sensitized Patients.","authors":"Jose L Estrada, Luz M Reyes, Zhang Yu Wang, Chris Burlak, Victor Novara Gennuso, Ovidio Figueroa, Coral Levkovitz, Rodrigo M Vianna, Sabrina Copsel, Matt Tector, A Joseph Tector","doi":"10.1097/TP.0000000000005385","DOIUrl":"10.1097/TP.0000000000005385","url":null,"abstract":"<p><strong>Background: </strong>The most common cause of late graft failure in renal allotransplantation is chronic antibody-mediated rejection caused by donor-specific antibodies against class II human leukocyte antigen (HLA), particularly HLA-DQ. In preclinical renal xenotransplantation, graft failure 1-mo posttransplant is characterized by glomerulopathy and immunoglobulin G (IgG) staining in the glomerulus. Rhesus renal xenograft recipients with late graft failure also have anti-swine leukocyte antigen (SLA)-DQ antibodies present in their serum suggesting that, like allotransplantation, late xenograft failure may be driven by antidonor major histocompatibility complex class II antibodies, particularly SLA-DQ. Some patients have anti-SLA-DQ antibodies, but the magnitude of this problem is unclear.</p><p><strong>Methods: </strong>We evaluated patient sera for the presence of anti-SLA-DQ antibodies in engineered immortalized cells, to determine patients' reactivity toward 7 different SLA-DQ molecules. Next, we created glycoprotein, alpha-galactosyltransferase 1/beta-1,4-N-acetyl-galactosaminyltransferase 2/SLA-DQ knockout (KO) pigs so that we could evaluate the impact of SLA-DQ on the level of antipig antibodies by performing crossmatches with serum from naïve and HLA class II-sensitized patients and SLA-DQ KO peripheral blood mononuclear cells.</p><p><strong>Results: </strong>Naïve and HLA class II-sensitized patients had anti-SLA-DQ immunoglobulin M and IgG that were pan-specific rather than SLA-DQ allele-specific. Crossmatching patient sera with peripheral blood mononuclear cells from the SLA-DQ KO pigs revealed that many patients had anti-SLA-DQ antibodies. Eliminating SLA-DQ reduced human immunoglobulin M and IgG binding to primary pig cells.</p><p><strong>Conclusions: </strong>SLA-DQ is a xenoantigen for most patients. SLA-DQ KO pigs may help address this problem.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1357-1366"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701606","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}

{"title":"A Map and a Primitive Blueprint for Moving Ahead With Clinical Xenotransplantation.","authors":"A Joseph Tector","doi":"10.1097/TP.0000000000005457","DOIUrl":"10.1097/TP.0000000000005457","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1284-1285"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249727","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}

{"title":"Difference Between LDLT and DDLT in Predicting Early Graft Function.","authors":"Akihiko Soyama, Susumu Eguchi","doi":"10.1097/TP.0000000000005319","DOIUrl":"10.1097/TP.0000000000005319","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1286-1287"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068247","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}

{"title":"Inactivating the Innate Immune Receptor CD11b With a First-in-class Monoclonal Antibody Prolongs the Survival of Kidney Allografts in Nonhuman Primates.","authors":"Abbas Dehnadi, Ivy A Rosales, Jian-Ping Xiong, Tatsuo Kawai, Hyshem H Lancia, Gilles Benichou, Robert B Colvin, A Benedict Cosimi, M Amin Arnaout","doi":"10.1097/TP.0000000000005370","DOIUrl":"10.1097/TP.0000000000005370","url":null,"abstract":"<p><strong>Backgournd: </strong>Peritransplant ischemia/reperfusion injury (IRI) plays a central pathogenic role in nondelayed or delayed kidney allograft function immediately after transplantation and increases the risk of subsequent rejection. Potential therapies targeting specific cytokines or complement proteins to limit IRI have failed in clinical trials. Monoclonal antibody 107 (mAb107), a \"pure\" (nonactivating) inhibitor of the archetypal innate immune receptor integrin CD11b, has been shown to extend the survival of IRI nonhuman primate native kidneys in an in situ model.</p><p><strong>Methods: </strong>Here, we administered mAb107 before allograft revascularization to determine its efficacy for extending the survival of ischemia-damaged donor kidneys transplanted into major histocompatibility complex-mismatched nonhuman primate recipients.</p><p><strong>Results: </strong>We observed a significant delay in the onset of rejection and prolongation of allograft survival in mAb107-treated versus control recipients. Early allograft biopsies suggest this is secondary to the selective suppression of infiltrating neutrophils and macrophages.</p><p><strong>Conclusions: </strong>These observations support the hypothesis that inactivating CD11b with mAb107 may provide an effective strategy for prolonging the survival of ischemia-damaged allografts and increasing the successful use of marginal donor organs.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1350-1356"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587184","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}

{"title":"Heterogeneity of Non-HLA Antibody Prevalence in Kidney Antibody-mediated Rejection With the Commercial Luminex Assays.","authors":"Bogdan Obrișcă, Nicolae Leca, Elaine Chou-Wu, Lena Sibulesky, Ramasamy Bakthavatsalam, Catherine E Kling, Rasha Alawieh, Kelly D Smith, Gener Ismail, Idoia Gimferrer","doi":"10.1097/TP.0000000000005363","DOIUrl":"10.1097/TP.0000000000005363","url":null,"abstract":"<p><strong>Background: </strong>The current state of non-HLA antibody testing in antibody-mediated rejection (AMR) remains not standardized and controversial.</p><p><strong>Methods: </strong>We used 2 different commercial solid-phase assays to investigate the presence of non-HLA antibodies in a cohort of kidney transplant recipients stratified according to biopsy-proven AMR and HLA-donor-specific antibody status.</p><p><strong>Results: </strong>Assay 1 and 2 evaluated 60 and 39 different non-HLAs, of which 25 were shared. From the 25 common antigens, only 36% (n = 9) have a moderate correlation ( r ≥ 0.6) in signal intensity. We observed significant heterogeneity in the prevalence of specific non-HLA antibodies detected between assay 1 and 2. Furthermore, the 2 assays showed substantial differences in the quantities, as well as specificities, of the positive non-HLA antibodies in each patient. Overall, the number of patients with positive antibodies that were detected by both assays was relatively low (median, 5 patients [interquartile range, 3-8] and 6 patients [interquartile range, 3-10] for transplant and biopsy samples, respectively, according to different antigens). Additionally, the panel of specific non-HLA antibodies found associated with AMR (and specifically with AMR/HLA donor-specific antibody negative) and graft loss was assay dependent.</p><p><strong>Conclusions: </strong>We have shown that the current non-HLA antibody assays exhibit significant heterogeneity in terms of antibodies identified per patient and in association with rejection and graft loss.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e409-e421"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701618","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}

{"title":"Belgian Consensus Guidelines Within Eurotransplant on Imlifidase-enabled Deceased Donor Kidney Transplantation in Highly Sensitized Patients.","authors":"Dirk R J Kuypers, Frans H J Claas, Antoine Bouquegneau, Antoine Buemi, Johan W de Fijter, Marie-Paule Emonds, Giuseppe Gambino, Thibaut Gervais, André Gothot, Vanda Holovska, Alain Le Moine, Annick Massart, Dimitri Mikhalski, Maarten Naesens, Lissa Pipeleers, Justine Schmitt, Corentin Streel, Steven Van Laecke, Laurent Weekers, Karl Martin Wissing, Nada Kanaan","doi":"10.1097/TP.0000000000005388","DOIUrl":"10.1097/TP.0000000000005388","url":null,"abstract":"<p><p>Highly sensitized (HS) kidney transplant (KTx) candidates, that is, typically considered internationally as those with panel-reactive antibody levels of >85%, remain a substantial subpopulation of patients with low chance of receiving a compatible organ. Among its many objectives, Eurotransplant-an international transplant organ allocation network serving 8 European countries-aims to improve the management of HS KTx candidates through its prioritized \"acceptable mismatch\" (AM) program. However, despite this program, some HS patients within the Eurotransplant network who have panel-reactive antibodies >85% still cannot access donor kidneys. For patients who remain in the AM program for ≥3 y without undergoing transplantation, an additional prioritization strategy has been implemented. This involves defining further AMs to allow for desensitization with imlifidase within the AM program. While the AM desensitization program was being developed, the Belgian Imlifidase Scientific Expert Group within the Eurotransplant network independently recognized the need for guidelines on imlifidase desensitization for real-world use in HS KTx candidates (including both AM and Eurotransplant Kidney Allocation System patients). This article describes the consensus guidelines they subsequently developed, which represent a model that any center within the Eurotransplant region could adapt or apply in clinical practice when treating HS KTx candidates who require imlifidase desensitization. The consensus guidelines include patient eligibility criteria for imlifidase treatment that align with Eurotransplant allocation rules and incorporate posttransplant management strategies for HS patients. These guidelines are dynamic and will be reviewed and updated regularly as Eurotransplant rules change and imlifidase experience grows.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1274-1283"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046004","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}

{"title":"Equity in Access to Kidney Transplantation: Policy Change Is Necessary But Not Enough.","authors":"Joy E Obayemi, Dinee C Simpson","doi":"10.1097/TP.0000000000005425","DOIUrl":"10.1097/TP.0000000000005425","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1292-1293"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112178","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}