Clinical transplants最新文献_第9页

Late Antibody-Mediated Rejection in a Large Prospective Cross-Sectional Study of Kidney Allograft Recipients--Preliminary Results of the Screening Phase of the BORTEJECT Trial. 在一项大型前瞻性横断面研究中，肾移植受者的晚期抗体介导的排斥反应——BORTEJECT试验筛选阶段的初步结果。

Clinical transplants Pub Date : 2014-01-01

Farsad Eskandary, Gregor Bond, Heinz Regele, Nicolas Kozakowski, Zeljko Kikić, Markus Wahrmann, Helmuth Haslacher, Rainer Oberbauer, Vido Ramassar, Philip Halloran, Georg A Böhmig

{"title":"Late Antibody-Mediated Rejection in a Large Prospective Cross-Sectional Study of Kidney Allograft Recipients--Preliminary Results of the Screening Phase of the BORTEJECT Trial.","authors":"Farsad Eskandary, Gregor Bond, Heinz Regele, Nicolas Kozakowski, Zeljko Kikić, Markus Wahrmann, Helmuth Haslacher, Rainer Oberbauer, Vido Ramassar, Philip Halloran, Georg A Böhmig","doi":"","DOIUrl":"","url":null,"abstract":"There is limited data on the rate of late antibody-mediated rejection (ABMR) in unselected transplant cohorts. Here, we investigated the prevalence and characteristics of ABMR in a large cohort of long-term kidney allograft recipients. Patients were screened in the context of a randomized controlled trial (BORTEJECT study; ClinicalTrials.gov: NCT01873157) designed to investigate the impact of bortezomib on the course of late ABMR. The study (initiation in October 2013) includes a cross-sectional ABMR screening (key inclusion criterion: functioning graft at ≥ 180 days) to identify 44 recipients eligible for inclusion in the intervention trial. Patients were screened for donor-specific antibodies (DSA) applying solid phase technology and DSA+ recipients underwent protocol biopsies. Through November 2014, ABMR screening (after a median of 6.5 years post-transplantation) had been completed for 714 recipients. One hundred one patients (14%) had DSA above a threshold of 1,000 mean fluorescence intensity (MFI). Forty-four of 78 DSA+ recipients (6% of the overall cohort) subjected to biopsy were diagnosed with C4d-positive (n = 17) or -negative (n = 27) ABMR and 40 consented to participate in the intervention trial. DSA+ABMR+ and DSA+ABMR- patients differed significantly with respect to the MFI of the highest level DSA (P < 0.001), whereby ABMR or C4d positivity were moderately predicted by MFI values (area under the receiver operating characteristic curve: 0.75 and 0.84, respectively). In conclusion, the results of this cross-sectional analysis suggest a ≥ 6% prevalence of late ABMR. We demonstrate that the more frequent finding of circulating DSA may not necessarily associate with ABMR diagnosis, especially in patients with low antibody levels.","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":" ","pages":"189-95"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33996232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel strategies for immunological monitoring of kidney transplant recipients: from microRNA to alloantibodies. 肾移植受体免疫监测的新策略:从microRNA到同种异体抗体。

Clinical transplants Pub Date : 2013-01-01

Sebastiaan Heidt, Michael Eikmans, Dave L Roelen, Frans H J Claas

引用次数: 0

Plasma cell biology: principles for therapeutic design. 浆细胞生物学:治疗设计原则。

Clinical transplants Pub Date : 2013-01-01

E Steve Woodle, Rita R Alloway, Nicole Schmidt Ejaz

{"title":"Plasma cell biology: principles for therapeutic design.","authors":"E Steve Woodle, Rita R Alloway, Nicole Schmidt Ejaz","doi":"","DOIUrl":"","url":null,"abstract":"Plasma cells represent the terminally differentiated cell population of the B-lymphocyte lineage. Plasma cells possess a unique biology, primarily as a result of their role as antibody factories. The unique features associated with the massive antibody production capacity confer upon the plasma cell a vulnerability to attack by specific targeted therapies. Over the past nine years, we have worked to develop therapies that exploit the unique features of plasma cells - therapies we have termed plasma cell targeted therapies. To date, these therapies have been almost exclusively based on proteasome inhibitor therapy, which has been used to treat antibody-mediated rejection and also to reduce chronic human leukocyte antigen antibody production via therapies commonly referred to as \"desensitization.\" Future iterations of plasma cell targeted regimens, however, are more likely to depend on combination therapies designed specifically to achieve additivity and preferably synergy, using either small molecule inhibitors of metabolic pathways or alternatively, biologic agents. As such, these plasma cell targeted therapies provide a new approach for treating acute and chronic antibody responses in humans, not only in transplantation, but also in other disease states including autoimmune disease.","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":" ","pages":"277-83"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32561747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incidence and hazards of alloantibodies in renal transplantation. 肾移植中同种异体抗体的发生率和危害。

Clinical transplants Pub Date : 2013-01-01

Matthew J Everly

引用次数: 0

Fifty years later. 五十年后。

Clinical transplants Pub Date : 2013-01-01

Terry L Mangan, Kathleen A Benedetti, Thomas E Starzl

引用次数: 0

Impact of solid phase antibody testing on organ allocation in the United States. 固相抗体检测对美国器官分配的影响。

Clinical transplants Pub Date : 2013-01-01

Nancy L Reinsmoen

{"title":"Impact of solid phase antibody testing on organ allocation in the United States.","authors":"Nancy L Reinsmoen","doi":"","DOIUrl":"","url":null,"abstract":"The implementation of the solid phase antibody assays has allowed for the detection and characterization of human leukocyte antigen (HLA) specific antibodies with greater sensitivity and specificity. This information can then be used along with the donor's HLA typing to predict crossmatch results (a virtual crossmatch). Using these data and the level of immunological risk assessed to the antibodies detected, the determination of unacceptable antigens can be made. The calculated panel reactive antibody (CPRA) provides for a means to determine the frequency of these unacceptable antigens in the donor population and thereby predict the probability of a positive crossmatch. In 2009, the Organ Procurement Transplant Network administered by the United Network for Organ Sharing adopted the CPRA as the means to define sensitization and to assign allocation points. Follow-up studies have shown that the number of organ offers refused due to a positive crossmatch has decreased significantly and has saved money through the elimination of unnecessary testing. An additional benefit has been the increased number of sensitized patients being transplanted successfully. Through technical improvements and the refined interpretation of the solid phase antibody assays, continual progress is being made in the definition of the unacceptable antigens and the ability to transplant sensitized patients.","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":" ","pages":"393-8"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32562699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donor specific antibodies before and after kidney transplant: the University of Colorado Experience. 肾移植前后供体特异性抗体:科罗拉多大学的经验。

Clinical transplants Pub Date : 2013-01-01

James E Cooper, Jane Gralla, Oluwafisayo Adebiyi, Alexander C Wiseman, Laurence Chan

{"title":"Donor specific antibodies before and after kidney transplant: the University of Colorado Experience.","authors":"James E Cooper, Jane Gralla, Oluwafisayo Adebiyi, Alexander C Wiseman, Laurence Chan","doi":"","DOIUrl":"","url":null,"abstract":"We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.22), although acute rejection occurred earlier in the DSA+ group. De novo DSA was detected in 65 of 261 patients (27%). All DSA was detected within the first posttransplant year. While acute rejection was more likely in patients with de novo DSA (29% versus 9.5% in those with no DSA), prospective DSA screening failed to predict this outcome as DSA was detected at the time of or after a rejection episode in 16 of 19 patients with both DSA and acute rejection. Two-year estimated graft survival was significantly worse in patients with versus without DSA, but was identical when removing patients with a prior acute rejection episode from the analysis. We have used a protocol of high dose (5 gm/kg) intravenous immunoglobulin infused over the course of 6 months in patients with DSA and either chronic graft dysfunction or following a recent acute antibody mediated rejection (AMR) episode. DSA MFI was reduced by 18% from the time of initiation to last follow up. This effect was largely due to reductions in class I DSA (-37%) and DSA in patients with a recent acute AMR (-51.5%), with a minimal effect on class II DSA and DSA in patients with chronic graft dysfunction. Despite treatment directed at antibody-producing plasma cells, antibody levels either persisted or worsened with no improvement in graft function. Overall, DSA is more amendable to treatment when associated with a recent acute rejection event.","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":" ","pages":"407-12"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32562701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HLA-specific antibody distribution in renal transplant waiting list patients: utility of antigen frequency data in the definition of HLA-reactive epitopes. hla特异性抗体在肾移植等候名单患者中的分布:抗原频率数据在hla反应性表位定义中的效用

Clinical transplants Pub Date : 2013-01-01

David Lowe, James Jones, Derek Middleton

引用次数: 0

Immunoregulation and allogenicity in cardiac stem cell regenerative therapy. 心脏干细胞再生治疗中的免疫调节和异体性。

Clinical transplants Pub Date : 2013-01-01

Dominique Charron, Reem Al-Daccak

{"title":"Immunoregulation and allogenicity in cardiac stem cell regenerative therapy.","authors":"Dominique Charron, Reem Al-Daccak","doi":"","DOIUrl":"","url":null,"abstract":"Stem cell based strategies are fast track, novel, alternative therapies to repair damaged tissues of chronic diseases and have raised great hopes for incurable heart failure in particular. Various stem/progenitor populations are being put forward as potential therapies to achieve cardiac repair/regeneration. The recently described cardiac-derived progenitor/stem cells (CPC) received intensive investigation given their inherent programming to reconstitute the damaged myocardium. Clinical application of autologous cells provided convincing evidence of feasibility and efficiency but limited availability, and pointed out that the use of allogenic cells via cell banks, if proven safe, are a more realistic proposition for cardiac repair. Our recent findings reinforced this notion by demonstrating that the inherent immune features of human CPC shift their behavior within the allogenic settings towards the delivery of signals that promote the development, maintenance, and functioning of a PD-L1/PD1 mediated immune-modulator antiinflammatory reparative response, rather than a detrimental conventional allogenic process. In this context, we discuss how this allogenic immune response, if balanced, can be part of the dynamic and durable mechanisms proposed as critical to sustain cardiac regeneration and repair and propose, based on knowledge of transplantation practice strategies, to reach such balance.","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":" ","pages":"249-55"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32561743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exchange donor renal transplantation. 交换供肾移植。

Clinical transplants Pub Date : 2013-01-01

Soo Jin Kim, Myoung Soo Kim, Kiil Park

引用次数: 0