Patients receiving liver transplantation in a setting of complete portal vein (PV) and superior mesenteric vein (SMV) thrombosis (Yerdel grade 4) experience lower outcomes after surgery; prognosis is independently influenced by the portal flow reconstruction technique, showing better outcomes in physiological surgical strategies. We describe a case of living donor liver transplantation in which the patient could not receive common physiological reconstructions preoperatively due to multiple small collaterals and extensive thrombosis down to first branches of SMV. We performed thromboendovenectomy of the PV and SMV first, but acute thrombosis developed recurrently even with interposition venous homograft between pericholedochal collateral vein and proximal recipient PV. Immediate after surgery, an intervention radiologist performed stent insertion into 3 stenotic points. Through multidisciplinary approach, complete physiological recanalization was obtained with normal liver function.
{"title":"Unique multidisciplinary approach in living donor liver transplantation to achieve total physiological revascularization in a patient with complete occlusion of portal vein system with combined chronic and subacute thrombosis.","authors":"Francesca Albanesi, Jae-Yoon Kim, Kwang-Woong Lee, YoungRok Choi, Nam-Joon Yi, Suk-Kyun Hong, Kyung-Suk Suh","doi":"10.1016/j.ajt.2024.09.033","DOIUrl":"10.1016/j.ajt.2024.09.033","url":null,"abstract":"<p><p>Patients receiving liver transplantation in a setting of complete portal vein (PV) and superior mesenteric vein (SMV) thrombosis (Yerdel grade 4) experience lower outcomes after surgery; prognosis is independently influenced by the portal flow reconstruction technique, showing better outcomes in physiological surgical strategies. We describe a case of living donor liver transplantation in which the patient could not receive common physiological reconstructions preoperatively due to multiple small collaterals and extensive thrombosis down to first branches of SMV. We performed thromboendovenectomy of the PV and SMV first, but acute thrombosis developed recurrently even with interposition venous homograft between pericholedochal collateral vein and proximal recipient PV. Immediate after surgery, an intervention radiologist performed stent insertion into 3 stenotic points. Through multidisciplinary approach, complete physiological recanalization was obtained with normal liver function.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378812","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}
Pub Date : 2024-10-03DOI: 10.1016/j.ajt.2024.09.025
Elizabeth D Knackstedt, Sarah G Anderson, Ravinder Anand, Jeff Mitchell, Ronen Arnon, Linda Book, Udeme Ekong, Scott A Elisofon, Katryn Furuya, Ryan Himes, Ajay K Jain, Nadia Ovchinsky, Shikha S Sundaram, John Bucuvalas, Lara Danziger-Isakov
Although cytomegalovirus (CMV) is a common complication after pediatric liver transplantation (PLT), the optimal method for CMV prevention is uncertain and lacks multi-centered investigation. We compared the effectiveness of short (<120d) versus long (>180d) CMV primary antiviral prophylaxis to prevent CMV disease in PLT, through a prospective cohort study of primary PLT (<18 yrs of age) recipients enrolled in the Society of Pediatric Liver Transplantation (SPLIT) registry from 2015 to 2019 with either donor or recipient CMV seropositivity. Participants were grouped into short or long prophylaxis based on their center's practice and intended duration. 199 PLT recipients were enrolled including 112 (56.3%) short and 87 (43.7%) long prophylaxis. End-organ disease was rare and similar between groups (2.7% and 1.1%; p=0.45). CMV DNAemia and syndrome were more common in the short compared to long (26.8% v. 13.8%; p=0.03 and 18.8% v. 6.9%; p=0.02). Neutropenia occurred more commonly with long prophylaxis (55.2% vs. 16.1%; p<0.001). Graft and patient survival were similar. Consideration of a short prophylaxis must weigh increased risk of CMV syndrome/DNAemia against medication burden and neutropenia of longer prophylaxis.
{"title":"Cytomegalovirus (CMV) Prophylaxis in Pediatric Liver Transplantation (PLT): A Comparison of Strategies Across the SPLIT Consortium.","authors":"Elizabeth D Knackstedt, Sarah G Anderson, Ravinder Anand, Jeff Mitchell, Ronen Arnon, Linda Book, Udeme Ekong, Scott A Elisofon, Katryn Furuya, Ryan Himes, Ajay K Jain, Nadia Ovchinsky, Shikha S Sundaram, John Bucuvalas, Lara Danziger-Isakov","doi":"10.1016/j.ajt.2024.09.025","DOIUrl":"10.1016/j.ajt.2024.09.025","url":null,"abstract":"<p><p>Although cytomegalovirus (CMV) is a common complication after pediatric liver transplantation (PLT), the optimal method for CMV prevention is uncertain and lacks multi-centered investigation. We compared the effectiveness of short (<120d) versus long (>180d) CMV primary antiviral prophylaxis to prevent CMV disease in PLT, through a prospective cohort study of primary PLT (<18 yrs of age) recipients enrolled in the Society of Pediatric Liver Transplantation (SPLIT) registry from 2015 to 2019 with either donor or recipient CMV seropositivity. Participants were grouped into short or long prophylaxis based on their center's practice and intended duration. 199 PLT recipients were enrolled including 112 (56.3%) short and 87 (43.7%) long prophylaxis. End-organ disease was rare and similar between groups (2.7% and 1.1%; p=0.45). CMV DNAemia and syndrome were more common in the short compared to long (26.8% v. 13.8%; p=0.03 and 18.8% v. 6.9%; p=0.02). Neutropenia occurred more commonly with long prophylaxis (55.2% vs. 16.1%; p<0.001). Graft and patient survival were similar. Consideration of a short prophylaxis must weigh increased risk of CMV syndrome/DNAemia against medication burden and neutropenia of longer prophylaxis.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378811","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}
Pub Date : 2024-10-02DOI: 10.1016/j.ajt.2024.09.034
Jason B Doppenberg, Rutger M van Rooden, Madeleine C van Dijk, Femke H C de Goeij, Fenna J van der Heijden, Ian P J Alwayn, Eelco J P de Koning, Jeroen de Jonge, Marten A Engelse, Volkert A L Huurman
Abdominal normothermic regional perfusion (aNRP) is an in situ normothermic oxygenated donor perfusion technique before procurement during controlled donation after circulatory death (cDCD) procedures and allows for organ quality evaluation. There are few data on the effect of aNRP on pancreatic islet isolation and subsequent transplantation outcomes. We aim to evaluate the impact of aNRP on cDCD pancreatic islet isolation and transplantation. A retrospective analysis was performed on pancreatic islet isolation outcomes from aNRP, cDCD, and donation after brain death pancreases. Isolations were compared to previous donor age (60-75 years) matched isolations. Islet function was assessed by a dynamic glucose-stimulated insulin secretion. Donor baseline characteristics did not differ among groups. Isolations from aNRP pancreases (471 739 islet equivalents [IEQ] [655 435-244 851]) yielded more islets compared to cDCD (218 750 IEQ [375 951-112 364], P < .01) and to donation after brain death (206 522 IEQ [385 544-142 446], P = .03) pancreases. Dynamic glucose-stimulated insulin secretion tests in 7 aNRP islet preparations showed a mean stimulation index of 4.91, indicating good functionality. Bilirubin and alanine aminotransferase during aNRP correlated with islet yield (r2 = 0.685, P = .002; r2 = 0.491, P = .016, respectively). Islet isolation after aNRP in cDCD donors results in a high islet yield with viable functional islets. aNRP could increase the utilization of the pancreases for islet transplantation.
{"title":"Abdominal normothermic regional perfusion after donation after circulatory death improves pancreatic islet isolation yield.","authors":"Jason B Doppenberg, Rutger M van Rooden, Madeleine C van Dijk, Femke H C de Goeij, Fenna J van der Heijden, Ian P J Alwayn, Eelco J P de Koning, Jeroen de Jonge, Marten A Engelse, Volkert A L Huurman","doi":"10.1016/j.ajt.2024.09.034","DOIUrl":"10.1016/j.ajt.2024.09.034","url":null,"abstract":"<p><p>Abdominal normothermic regional perfusion (aNRP) is an in situ normothermic oxygenated donor perfusion technique before procurement during controlled donation after circulatory death (cDCD) procedures and allows for organ quality evaluation. There are few data on the effect of aNRP on pancreatic islet isolation and subsequent transplantation outcomes. We aim to evaluate the impact of aNRP on cDCD pancreatic islet isolation and transplantation. A retrospective analysis was performed on pancreatic islet isolation outcomes from aNRP, cDCD, and donation after brain death pancreases. Isolations were compared to previous donor age (60-75 years) matched isolations. Islet function was assessed by a dynamic glucose-stimulated insulin secretion. Donor baseline characteristics did not differ among groups. Isolations from aNRP pancreases (471 739 islet equivalents [IEQ] [655 435-244 851]) yielded more islets compared to cDCD (218 750 IEQ [375 951-112 364], P < .01) and to donation after brain death (206 522 IEQ [385 544-142 446], P = .03) pancreases. Dynamic glucose-stimulated insulin secretion tests in 7 aNRP islet preparations showed a mean stimulation index of 4.91, indicating good functionality. Bilirubin and alanine aminotransferase during aNRP correlated with islet yield (r<sup>2</sup> = 0.685, P = .002; r<sup>2</sup> = 0.491, P = .016, respectively). Islet isolation after aNRP in cDCD donors results in a high islet yield with viable functional islets. aNRP could increase the utilization of the pancreases for islet transplantation.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374731","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}
Pub Date : 2024-09-28DOI: 10.1016/j.ajt.2024.09.032
Audrey E Brown, Yvonne M Kelly, Arya Zarinsefat, Raphael P H Meier, Giulia Worner, Mehdi Tavakol, Minnie M Sarwal, Zoltan G Laszik, Peter G Stock, Tara K Sigdel
Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in "omics" methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score's relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (P < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes' infiltration. Significantly higher tCRM scores were found in grade 3 ACR (P = .007) and grade 2 ACR (P = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.
{"title":"Gene expression-based molecular scoring of pancreas transplant rejection for a quantitative assessment of rejection severity and resistance to treatment.","authors":"Audrey E Brown, Yvonne M Kelly, Arya Zarinsefat, Raphael P H Meier, Giulia Worner, Mehdi Tavakol, Minnie M Sarwal, Zoltan G Laszik, Peter G Stock, Tara K Sigdel","doi":"10.1016/j.ajt.2024.09.032","DOIUrl":"10.1016/j.ajt.2024.09.032","url":null,"abstract":"<p><p>Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in \"omics\" methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score's relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (P < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes' infiltration. Significantly higher tCRM scores were found in grade 3 ACR (P = .007) and grade 2 ACR (P = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337685","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}
Pub Date : 2024-09-27DOI: 10.1016/j.ajt.2024.03.029
{"title":"Portal inflow for liver transplantation when there is extensive portal and mesenteric thrombus","authors":"","doi":"10.1016/j.ajt.2024.03.029","DOIUrl":"10.1016/j.ajt.2024.03.029","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328326","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}
Pub Date : 2024-09-27DOI: 10.1016/j.ajt.2024.09.031
Steve Chadban, Kymberly D Watt
{"title":"When is it safe to transplant after cancer-adding data to the decision.","authors":"Steve Chadban, Kymberly D Watt","doi":"10.1016/j.ajt.2024.09.031","DOIUrl":"10.1016/j.ajt.2024.09.031","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337687","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}
Pub Date : 2024-09-27DOI: 10.1016/j.ajt.2024.09.030
Thei S Steenvoorden, Lara Evers, Liffert Vogt, Janneke A J Rood, Jesper Kers, Marije C Baas, Maarten H L Christiaans, Jan H N Lindeman, Jan-Stephan F Sanders, Aiko P J de Vries, Arjan D van Zuilen, Frederike J Bemelman, Hessel Peters-Sengers
Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.
{"title":"The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry.","authors":"Thei S Steenvoorden, Lara Evers, Liffert Vogt, Janneke A J Rood, Jesper Kers, Marije C Baas, Maarten H L Christiaans, Jan H N Lindeman, Jan-Stephan F Sanders, Aiko P J de Vries, Arjan D van Zuilen, Frederike J Bemelman, Hessel Peters-Sengers","doi":"10.1016/j.ajt.2024.09.030","DOIUrl":"10.1016/j.ajt.2024.09.030","url":null,"abstract":"<p><p>Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337686","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}
Pub Date : 2024-09-26DOI: 10.1016/j.ajt.2024.09.028
Daniel J Ahn, Allison J Kwong, Anji E Wall, William F Parker
In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board's implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (P < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; P = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (P < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.
{"title":"Association of nonstandardized model for end-stage liver disease score exceptions with waitlist mortality in adult liver transplant candidates.","authors":"Daniel J Ahn, Allison J Kwong, Anji E Wall, William F Parker","doi":"10.1016/j.ajt.2024.09.028","DOIUrl":"10.1016/j.ajt.2024.09.028","url":null,"abstract":"<p><p>In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board's implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (P < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; P = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (P < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337684","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}
NK cell-mediated antibody-dependent cell cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. FCGR3A V176/F176 polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q13/STP13 polymorphism, was never investigated in kidney transplantation. To assess the clinical relevance of FCGR2C Q13/STP13 polymorphism in conjunction with FCGR3A V176/F176 polymorphism, 242 kidney transplant recipients were genotyped. NK cell FcγR expression and ADCC activity were assessed. RNA sequencing was performed on kidney allograft biopsies to explore the presence of infiltrating FcγR+ NK cells. The FCGR2C Q13 allele was enriched in antibody-mediated rejection (ABMR) patients. FcγRIIc Q13+ NK cells had higher ADCC activity than FcγRIIc Q13- NK cells. In combination with the high-affinity FCGR3A V176 allele, Q13+V176+ NK cells were the most functionally potent. Q13+ was associated with worse microvascular inflammation and a higher risk of allograft loss. Among V176- patients, previously described in the literature as lower risk patients, Q13+V176- showed a lower graft survival than Q13-V176- patients. In ABMR biopsies, FCGR2C transcripts were enriched and associated with ADCC-related transcripts. Our results suggest that FCGR2C Q13 in addition to FCGR3A V176 is a significant risk allele that may enhance NK cell-mediated ADCC and contribute to allograft injury and poor survival.
NK 细胞介导的抗体依赖性细胞毒性(ADCC)是体液同种异体移植损伤的主要机制。FCGR3A V176/F176 多态性会影响 ADCC 活性。此外,由 Q13/STP13 多态性决定的 NK 细胞 FcγRIIc 表达在肾移植中从未被研究过。为了评估FCGR2C Q13/STP13多态性与FCGR3A V176/F176多态性的临床相关性,对242名肾移植受者进行了基因分型。对 NK 细胞 FcγR 表达和 ADCC 活性进行了评估。对肾移植活组织进行了 RNA 测序,以探究是否存在浸润的 FcγR+ NK 细胞。FCGR2C Q13等位基因在抗体介导的排斥反应(ABMR)患者中富集。FcγRIIc Q13+ NK细胞的ADCC活性高于FcγRIIc Q13- NK细胞。与高亲和力的 FCGR3A V176 等位基因结合,Q13+V176+ NK 细胞的功能最强。Q13+与更严重的微血管炎症和更高的异体移植损失风险有关。在以前文献中被描述为低风险患者的 V176- 患者中,Q13+V176- 患者的移植物存活率低于 Q13-V176- 患者。在ABMR活检中,FCGR2C转录本富集并与ADCC相关转录本相关。我们的研究结果表明,除FCGR3A V176外,FCGR2C Q13也是一个重要的风险等位基因,它可能会增强NK细胞介导的ADCC,导致异体移植物损伤和存活率低下。
{"title":"FCGR2C Q13 and FCGR3A V176 alleles jointly associate with worse NK-cell mediated antibody-dependent cellular cytotoxicity and microvascular inflammation in kidney allograft antibody-mediated rejection.","authors":"Elodie Bailly,Camila Macedo,Xinyan Gu,Deborah Hollingshead,Carol Bentlejewski,Erica Fong,Penelope A Morel,Parmjeet Randhawa,Adriana Zeevi,Carmen Lefaucheur,Diana Metes","doi":"10.1016/j.ajt.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.018","url":null,"abstract":"NK cell-mediated antibody-dependent cell cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. FCGR3A V176/F176 polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q13/STP13 polymorphism, was never investigated in kidney transplantation. To assess the clinical relevance of FCGR2C Q13/STP13 polymorphism in conjunction with FCGR3A V176/F176 polymorphism, 242 kidney transplant recipients were genotyped. NK cell FcγR expression and ADCC activity were assessed. RNA sequencing was performed on kidney allograft biopsies to explore the presence of infiltrating FcγR+ NK cells. The FCGR2C Q13 allele was enriched in antibody-mediated rejection (ABMR) patients. FcγRIIc Q13+ NK cells had higher ADCC activity than FcγRIIc Q13- NK cells. In combination with the high-affinity FCGR3A V176 allele, Q13+V176+ NK cells were the most functionally potent. Q13+ was associated with worse microvascular inflammation and a higher risk of allograft loss. Among V176- patients, previously described in the literature as lower risk patients, Q13+V176- showed a lower graft survival than Q13-V176- patients. In ABMR biopsies, FCGR2C transcripts were enriched and associated with ADCC-related transcripts. Our results suggest that FCGR2C Q13 in addition to FCGR3A V176 is a significant risk allele that may enhance NK cell-mediated ADCC and contribute to allograft injury and poor survival.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329263","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}
Pub Date : 2024-09-25DOI: 10.1016/j.ajt.2024.09.027
Matthew M Byrne,Mariana Chávez-Villa,Luis I Ruffolo,Anthony Loria,Yutaka Endo,Amber Niewiemski,Cristina Jimenez-Soto,Jennifer I Melaragno,Ramaraju Gopal,Priya D Farooq,Richard F Dunne,Karen Pineda-Solis,Amit Nair,Mark Orloff,Koji Tomiyama,Roberto Hernandez-Alejandro
Living donor liver transplantation (LDLT) is a treatment option for select patients with unresectable colorectal liver metastasis (uCRLM). We describe our center's experience of patient selection, insurance approval, and outcomes after LDLT after first referral in March 2019. Of the 206 evaluated patients, twenty-three underwent LDLT. We found that patients who were referred earlier in their oncologic course were more likely to be eligible for transplantation. After completion of the Rochester Protocol for LDLT eligibility, recipients had a median delay of care of 10 days (IQR 0-36) related to insurance appeal, with six patients (30%) having a delay longer than 30 days. LDLT recipients had an overall survival proportion of 100% and 91% at 1, and 3 years; and a recurrence-free survival proportion of 100% and 40%, at 1 and 3 years, respectively. All donors underwent right hepatectomy, of which only one donor had a Clavien-Dindo IIIa complication and readmission. There was no donor mortality. We assert that multidisciplinary care and strict patient selection through the Rochester Protocol were paramount to our center's success. In the appropriately selected patient, LDLT for uCRLM may be justified, and patients should be referred to transplant oncology centers for evaluation.
{"title":"The Rochester Protocol for Living Donor Liver Transplantation of Unresectable Colorectal Liver Metastasis: A 5-Year Report on Selection, Approval, and Outcomes.","authors":"Matthew M Byrne,Mariana Chávez-Villa,Luis I Ruffolo,Anthony Loria,Yutaka Endo,Amber Niewiemski,Cristina Jimenez-Soto,Jennifer I Melaragno,Ramaraju Gopal,Priya D Farooq,Richard F Dunne,Karen Pineda-Solis,Amit Nair,Mark Orloff,Koji Tomiyama,Roberto Hernandez-Alejandro","doi":"10.1016/j.ajt.2024.09.027","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.027","url":null,"abstract":"Living donor liver transplantation (LDLT) is a treatment option for select patients with unresectable colorectal liver metastasis (uCRLM). We describe our center's experience of patient selection, insurance approval, and outcomes after LDLT after first referral in March 2019. Of the 206 evaluated patients, twenty-three underwent LDLT. We found that patients who were referred earlier in their oncologic course were more likely to be eligible for transplantation. After completion of the Rochester Protocol for LDLT eligibility, recipients had a median delay of care of 10 days (IQR 0-36) related to insurance appeal, with six patients (30%) having a delay longer than 30 days. LDLT recipients had an overall survival proportion of 100% and 91% at 1, and 3 years; and a recurrence-free survival proportion of 100% and 40%, at 1 and 3 years, respectively. All donors underwent right hepatectomy, of which only one donor had a Clavien-Dindo IIIa complication and readmission. There was no donor mortality. We assert that multidisciplinary care and strict patient selection through the Rochester Protocol were paramount to our center's success. In the appropriately selected patient, LDLT for uCRLM may be justified, and patients should be referred to transplant oncology centers for evaluation.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329254","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}