TransplantationPub Date : 2025-07-01Epub Date: 2024-12-03DOI: 10.1097/TP.0000000000005258
Jason F Goldberg, Christopher R deFilippi, Christopher Lockhart, Erick R McNair, Shashank S Sinha, Hyesik Kong, Samer S Najjar, Brendan J Lohmar, Inna Tchoukina, Keyur Shah, Erika Feller, Steven Hsu, Maria E Rodrigo, Moonkyoo Jang, Charles C Marboe, Gerald J Berry, Hannah A Valantine, Sean Agbor-Enoh, Palak Shah
{"title":"Proteomics in Acute Heart Transplant Rejection, on Behalf of the GRAfT Investigators.","authors":"Jason F Goldberg, Christopher R deFilippi, Christopher Lockhart, Erick R McNair, Shashank S Sinha, Hyesik Kong, Samer S Najjar, Brendan J Lohmar, Inna Tchoukina, Keyur Shah, Erika Feller, Steven Hsu, Maria E Rodrigo, Moonkyoo Jang, Charles C Marboe, Gerald J Berry, Hannah A Valantine, Sean Agbor-Enoh, Palak Shah","doi":"10.1097/TP.0000000000005258","DOIUrl":"10.1097/TP.0000000000005258","url":null,"abstract":"<p><strong>Background: </strong>Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.</p><p><strong>Methods: </strong>Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.</p><p><strong>Results: </strong>Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR). Differential expression was found in 2 proteins during ACR (inflammatory proteins CXCL10 and CD5) and 73 proteins during AMR. The most abundant AMR proteins were the heart failure biomarkers N-terminal pro-B-type natriuretic peptide and suppression of tumorigenicity 2. In univariate logistic regression, odds of identifying ACR on endomyocardial biopsy increased with doubling of CXCL10 (odds ratio [OR] 2.2 [95% confidence interval (CI), 1.3-3.6]) and CD5 (OR 4.7 [95% CI, 1.7-12.9]) concentrations, and odds of AMR increased with doubling of N-terminal pro-B-type natriuretic peptide (OR 13.0 [95% CI, 2.7-62.7) and suppression of tumorigenicity 2 (OR 4.8 [95% CI, 2.1-10.7]) concentrations. After multivariable analysis with clinical covariates, these proteins showed similar odds of ACR or AMR on biopsy. Pathway analysis identified T cell-receptor signaling and cell differentiation as key pathways in ACR and cardiovascular disease and cell turnover in AMR.</p><p><strong>Conclusions: </strong>Proteomic analysis reveals unique biomarkers and biological pathway expression in ACR and AMR. Cardiac injury-associated biomarkers were more pronounced in AMR, whereas inflammatory biomarkers were more pronounced in ACR. Proteomic analysis may provide insights into rejection pathophysiology, detection, and therapy.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1230-1240"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772516","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}
TransplantationPub Date : 2025-07-01Epub Date: 2025-01-31DOI: 10.1097/TP.0000000000005346
Stephan Ensminger
{"title":"Protein Expression Profiling: At the Crossroads Between AMR and ACR?","authors":"Stephan Ensminger","doi":"10.1097/TP.0000000000005346","DOIUrl":"10.1097/TP.0000000000005346","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e346-e347"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068267","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}
TransplantationPub Date : 2025-07-01Epub Date: 2025-03-06DOI: 10.1097/TP.0000000000005355
Carol Li, Sheavonnie Wright, Perola Lamba, Mingming Zhou, Hua Xu, Vijay Sharma, Surya Seshan, Evgeniya Vaskova, Nimisha Sulejmani, Ian Schillebeeckx, Darshana Dadhania, Thangamani Muthukumar, Robert Woodward, Manikkam Suthanthiran
{"title":"Impact of Ultrasound-guided Percutaneous Core Needle Biopsy on Biomarkers of Human Kidney Allograft Status.","authors":"Carol Li, Sheavonnie Wright, Perola Lamba, Mingming Zhou, Hua Xu, Vijay Sharma, Surya Seshan, Evgeniya Vaskova, Nimisha Sulejmani, Ian Schillebeeckx, Darshana Dadhania, Thangamani Muthukumar, Robert Woodward, Manikkam Suthanthiran","doi":"10.1097/TP.0000000000005355","DOIUrl":"10.1097/TP.0000000000005355","url":null,"abstract":"<p><strong>Background: </strong>Deciphering the impact of invasive percutaneous core needle biopsy of the kidney allograft on diagnostic biomarkers may help guide their clinical usage.</p><p><strong>Methods: </strong>We prospectively enrolled 39 adult kidney allograft recipients (patients) who underwent 41 clinically indicated, ultrasound-guided, percutaneous core needle biopsies. Pre- and post-biopsy urines were analyzed for urinary cell 3-gene signature score (UroMap), and the bloods for peripheral blood gene expression score (AlloMap Kidney) and plasma donor-derived cell-free DNA percentage (dd-cfDNA). We performed statistical analyses to compare pre- and post-biopsy values.</p><p><strong>Results: </strong>Median A260/A280 ratios of RNA from pre- and post-biopsy urines were 1.99 and 2.01, respectively; RNA yield, 0.78 versus 0.76 micrograms; and transcript copies of 18S rRNA, TGFβ1, CD3ε, CXCL10, and UroMap score were similar (all P > 0.05, Wilcoxon matched-pairs signed-rank test). The pre- and post-scores were very strongly correlated (Spearman's correlation coefficient [r s ]: 0.83, P < 0.0001). AlloMap Kidney scores in pre- and post-biopsy peripheral blood were similar ( P > 0.05) and strongly correlated (r s = 0.70, P < 0.0001). dd-cfDNA in post-biopsy plasma was higher than in pre-biopsy plasma (0.61% versus 0.26%, P = 0.004). The higher post-biopsy percentage was replicated in an independent cohort of 119 post-biopsy plasma collected from 105 patients with no rejection biopsies. To normalize the biopsy-associated increase, a correction factor of -0.36% was derived by subtracting the pre-biopsy dd-cfDNA percent from the post-biopsy percent.</p><p><strong>Conclusions: </strong>UroMap and AlloMap Kidney scores are not affected by the biopsy procedure. However, dd-cfDNA increases following the biopsy procedure and could be normalized using the correction factor identified in this study.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1209-1221"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574158","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}
TransplantationPub Date : 2025-07-01Epub Date: 2024-12-24DOI: 10.1097/TP.0000000000005301
Kristopher P Croome, Vijay Subramanian, Amit K Mathur, Bashar Aqel, Shennen A Mao, Jacob N Clendenon, Dana K Perry, Kiran Dhanireddy, C Burcin Taner
{"title":"Outcomes of DCD Liver Transplant Using Sequential Normothermic Regional Perfusion and Normothermic Machine Perfusion or NRP Alone Versus Static Cold Storage.","authors":"Kristopher P Croome, Vijay Subramanian, Amit K Mathur, Bashar Aqel, Shennen A Mao, Jacob N Clendenon, Dana K Perry, Kiran Dhanireddy, C Burcin Taner","doi":"10.1097/TP.0000000000005301","DOIUrl":"10.1097/TP.0000000000005301","url":null,"abstract":"<p><strong>Background: </strong>The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner.</p><p><strong>Methods: </strong>Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in \"marginal\" cases.</p><p><strong>Results: </strong>Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used ( P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56).</p><p><strong>Conclusions: </strong>The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in \"marginal\" cases.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1184-1190"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883036","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}
TransplantationPub Date : 2025-07-01Epub Date: 2024-12-11DOI: 10.1097/TP.0000000000005279
Olivier Désy, Marie-Pier Thivierge, Stéphanie Béland, Jean-Simon Desgagnés, François Bouchard-Boivin, Alcino Gama, Isabelle Houde, Isabelle Lapointe, Isabelle Côté, Julie Lesage, Sacha A De Serres
{"title":"A Risk Score Using a Cell-based Assay Predicts Long-term Over-immunosuppression Events in Kidney Transplant Recipients.","authors":"Olivier Désy, Marie-Pier Thivierge, Stéphanie Béland, Jean-Simon Desgagnés, François Bouchard-Boivin, Alcino Gama, Isabelle Houde, Isabelle Lapointe, Isabelle Côté, Julie Lesage, Sacha A De Serres","doi":"10.1097/TP.0000000000005279","DOIUrl":"10.1097/TP.0000000000005279","url":null,"abstract":"<p><strong>Background: </strong>Infections and cancer are major causes of premature death in organ recipients. However, there have been few advances in personalized immunosuppressive therapy. We previously reported that a cell-based assay measuring CD14 + 16 + tumor necrosis factor-α + monocytes after peripheral blood mononuclear cell (PBMC) incubation with Epstein-Barr virus peptides has a high sensitivity for detecting over-immunosuppression (OIS) events in kidney recipients in the short term. We aimed to develop a risk score for predicting long-term events.</p><p><strong>Methods: </strong>We studied 551 PBMC samples from 118 kidney recipients. Following random allocation to a testing and training set, we derived a risk function for the delineated tertiles of low, intermediate, and high risk of OIS based on age and CD14 + 16 + tumor necrosis factor-α + cells.</p><p><strong>Results: </strong>Patients were followed for a median of 6.3 y (25th-75th percentiles: 3.7-8.3 y). Of these, 40 (34%) experienced an OIS event. The validation indicated that the risk score was well calibrated, with an absolute risk of 21%, 41%, and 61% in the low-, intermediate-, and high-risk categories, respectively ( P = 0.03). In sensitivity analyses, the risk score was robust to alternative definitions of OIS ranging from mild to severe. In particular, when restricted to life-threatening OIS, the proportion of events varied from 5% to 27% among the low- and high-risk categories, respectively ( P = 0.01).</p><p><strong>Conclusions: </strong>Using a combination of age and in vitro PBMC response to Epstein-Barr virus peptides allows a substantial shift in the estimated risk of OIS events.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1191-1200"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814032","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}
TransplantationPub Date : 2025-07-01Epub Date: 2024-12-11DOI: 10.1097/TP.0000000000005306
Alan Zambeli-Ljepović, Ali B Abbasi, Peter J Altshuler
{"title":"Predicting Over-immunosuppression in Kidney Transplant Recipients: Steps Toward Precision Medicine.","authors":"Alan Zambeli-Ljepović, Ali B Abbasi, Peter J Altshuler","doi":"10.1097/TP.0000000000005306","DOIUrl":"10.1097/TP.0000000000005306","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1113-1114"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814054","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}
TransplantationPub Date : 2025-07-01Epub Date: 2025-01-16DOI: 10.1097/TP.0000000000005304
Simran Gupta, Matt V Biondi, Priyal J Shah, Matthew R Buras, Lavanya Kodali, David M H Chascsa, Holenarasipur R Vikram, Janis E Blair
{"title":"Outcomes of Coccidioides Seropositive Solid Organ Transplant Recipients After Self-discontinuation of Antifungal Prophylaxis: The EIA-IgM-only Conundrum.","authors":"Simran Gupta, Matt V Biondi, Priyal J Shah, Matthew R Buras, Lavanya Kodali, David M H Chascsa, Holenarasipur R Vikram, Janis E Blair","doi":"10.1097/TP.0000000000005304","DOIUrl":"10.1097/TP.0000000000005304","url":null,"abstract":"<p><strong>Background: </strong>Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive.</p><p><strong>Methods: </strong>We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non-lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls).</p><p><strong>Results: </strong>No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results ( P < 0.001).</p><p><strong>Conclusions: </strong>For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1251-1256"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012470","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}
TransplantationPub Date : 2025-07-01Epub Date: 2025-02-19DOI: 10.1097/TP.0000000000005344
M Veronica Dioverti, Robin K Avery
{"title":"Commentary on \"Human Papillomavirus (HPV) Infection and Cytological Atypia in Female Allogeneic Hematopoietic Stem Cell Transplantation Recipients\".","authors":"M Veronica Dioverti, Robin K Avery","doi":"10.1097/TP.0000000000005344","DOIUrl":"10.1097/TP.0000000000005344","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1119-1121"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450393","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}