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https://www.readbyqxmd.com/read/28638610/looking-for-the-needle-in-the-kidney-transplantation-haystack
#1
Josep M Cruzado, Edoardo Melilli
The diagnosis of acute rejection still relies on renal allograft biopsy. In fact, histological features including C4d staining can be useful to differentiate cellular and antibody-mediated acute rejection. However, the pathogenic mechanism to define the type of rejection is usually assessed by anti-HLA donor specific antibodies (DSA) monitoring. Suspicion of acute rejection is usually based on renal function deterioration. This method has low sensitivity. Moreover, creatinine increase follows graft injury and therefore the diagnosis is performed when there is an ongoing acute rejection...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28634772/the-effect-of-desensitization-therapy-in-kidney-transplantation
#2
Yong Chul Kim, Mi-Yeon Yu, Jung Pyo Lee, Hajeong Lee, Sang-Il Min, Jongwon Ha, Yon Su Kim
BACKGROUND: Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear. METHODS: We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group...
June 20, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28629951/immunogenicity-of-class-i-hla-but-not-preformed-low-mfi-donor-specific-antibodies-correlates-with-outcomes-after-first-renal-transplantation
#3
A Lobashevsky, W Goggins, K Rosner, T Taber
BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-)...
June 16, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28627046/donor-specific-antibodies-are-associated-with-micro-and-macrovascular-coronary-disease-restrictive-myocardial-damage-and-poor-outcome-in-heart-transplanted-patients
#4
Tor Skibsted Clemmensen, Pernille Koefoed-Nielsen, Lis-Ann Jensen, Steen Hvitfeldt Poulsen, Niels Ramsing Holm, Brian Bridal Løgstrup, Evald Høj Christiansen, Jouke Dijkstra, Kamilla Pernille Bjerre Valen, Hans Eiskjaer
AIMS: We examined the relationship between donor-specific HLA antibody (DSA) presence and graft function, hemodynamics, cardiac allograft vasculopathy (CAV), and major adverse cardiac events (MACE) in stable long-term heart-transplanted (HTx) patients. METHODS: Sera from 79 patients (median 7.5 years after HTx) were analyzed for DSA presence. Graft function was evaluated by echocardiography and right heart catheterization. CAV-burden was determined by coronary angiography, optical coherence tomography (OCT), and coronary flow velocity reserve (CFVR)...
June 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28626871/a-successful-living-donor-liver-re-transplantation-for-graft-failure-within-seven-days-due-to-acute-de-novo-donor-specific-anti-hla-antibody-mediated-rejection
#5
Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Kiyotomo Abe, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Hiroshi Yagi, Naoki Shimojima, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Yasushi Fuchimoto, Kaori Kameyama, Yuko Kitagawa, Tatsuo Kuroda
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28626773/hla-epitopes-the-targets-of-monoclonal-and-alloantibodies-defined
#6
REVIEW
Nadim El-Awar, Vadim Jucaud, Anh Nguyen
Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#7
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28613436/the-incremental-cost-of-incompatible-living-donor-kidney-transplant-a-national-cohort-analysis
#8
David Axelrod, Krista L Lentine, Mark A Schnitzler, Xun Luo, Huiling Xiao, Babak J Orandi, Allan Massie, Jacqueline Garonzik-Wang, Mark D Stegall, Stanley C Jordan, Jose Oberholzer, Ty B Dunn, Lloyd E Ratner, Sandip Kapur, Ronald P Pelletier, John P Roberts, Marc L Melcher, Pooja Singh, Debra L Sudan, Marc P Posner, Jose M El-Amm, Ron Shapiro, Matthew Cooper, George S Lipkowitz, Michael A Rees, Christopher L Marsh, Bashir R Sankari, David A Gerber, Paul W Nelson, Jason Wellen, Adel Bozorgzadeh, A Osama Gaber, Robert A Montgomery, Dorry L Segev
Incompatible living donor kidney transplant (ILDKT) has been established as an effective option for end stage renal disease (ESRD) patients with willing but HLA incompatible live donors, reducing mortality and improving quality of life. Depending upon antibody titer, ILDKT can require highly resource intensive procedure including intravenous immunoglobulin, plasma exchange and/or cell depleting antibody treatment as well as protocol biopsies and DSA testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT recipients (N=926) with varying antibody titers to matched compatible transplants (N=2762) performed between 2002-2011...
June 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28613392/donor-recipient-matching-based-on-predicted-recognizable-hla-epitopes-predicts-the-incidence-of-de-novo-donor-specific-hla-antibodies-following-renal-transplantation
#9
Nils Lachmann, Matthias Niemann, Petra Reinke, Klemens Budde, Danilo Schmidt, Fabian Halleck, Axel Pruß, Constanze Schönemann, Eric Spierings, Oliver Staeck
De novo donor-specific HLA antibodies (dnDSA) are recognized as risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2,787 consecutive kidney transplants performed 1995-2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay...
June 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28604384/antibody-mediated-rejection-across-solid-organ-transplants-manifestations-mechanisms-and-therapies
#10
Nicole M Valenzuela, Elaine F Reed
Solid organ transplantation is a curative therapy for hundreds of thousands of patients with end-stage organ failure. However, long-term outcomes have not improved, and nearly half of transplant recipients will lose their allografts by 10 years after transplant. One of the major challenges facing clinical transplantation is antibody-mediated rejection (AMR) caused by anti-donor HLA antibodies. AMR is highly associated with graft loss, but unfortunately there are few efficacious therapies to prevent and reverse AMR...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28597555/harnessing-scientific-and-technological-advances-to-improve-equity-in-kidney-allocation-policies
#11
Anat R Tambur, Benoit Audry, Corinne Antoine, Caroline Suberbielle, Denis Glotz, Christian Jacquelinet
We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αβ allelic variants, respectively, on calculated PRA and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαβ allelic (study) versus serologic (current practice) nomenclature. A significant (p<10(-4) ) decrease in cPRA was observed with higher impact for male versus female, and first transplant versus retransplant (p<10(-4) ), affecting mostly patients with moderate cPRA (30-80%)...
June 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28585912/anti-hla-antibodies-testing-on-solid-phase-comparative-evaluation-of-different-kit-vendors-through-luminex-technology
#12
Pellegrino Biagio Minucci, Marianna Resse, Chiara Sabia, Antonella Esposito, Gustavo De Iorio, Claudio Napoli
OBJECTIVES: For decades, the detection of anti-HLA antibodies in candidates for solid-organ transplant has been performed with the traditional complement-dependent cytotoxicity method; this assay has been then integrated with the introduction of solid-phase assays. Over the past 20 years, the Luminex assay has become the most widely used in clinical laboratories due to both increased sensitivity and specificity versus enzyme-linked immunosorbent assay. However, even the Luminex technique has shown some critical issues, and choosing the most reliable method still remains challenging...
June 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28585408/increased-risk-of-infection-associated-death-with-incompatible-kidney-transplantations
#13
Christian Morath, Martin Zeier, Caner Süsal
In times of organ shortage, transplantation over the blood group A/B and HLA antibody barriers helps increasing the living donor pool in kidney transplantation. Waiting times are reduced while patient survival may be improved. By desensitization, both blood group A/B as well as HLA antibodies are eliminated from the patient's circulation using plasmapheresis, double filtration plasmapheresis or selective or unselective immunoadsorption. In addition, antibody production and posttransplant antibody rebound are prevented by powerful immunosuppression and induction therapy with or without B-cell eliminating anti-CD20 antibody rituximab...
June 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28583566/influences-of-pre-formed-donor-specific-anti-human-leukocyte-antigen-antibodies-in-living-donor-renal-transplantation-results-with-graft-immunocomplex-capture-fluorescence-analysis
#14
T Nakamura, H Ushigome, K Watabe, Y Imanishi, K Masuda, T Matsuyama, S Harada, K Koshino, T Iida, S Nobori, N Yoshimura
BACKGROUND: Advances in immunosuppressants enable organ transplantation for sensitized patients. However, influences of pre-formed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have not been fully understood in renal transplantation (RT). On the other hand, immunocomplex capture fluorescence analysis (ICFA) is a reliable method to detect donor-specific anti-HLA antibodies and HLA antigen complexes. Graft ICFA can detect DSA in an allograft (g-DSA). METHODS: To elucidate the consequences of pre-formed DSA, 198 patients who underwent living-donor RT were enrolled for this study (observation period: 57...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28576578/understanding-solid-phase-hla-antibody-assays-and-the-value-of-mfi
#15
REVIEW
Harold C Sullivan, Howard M Gebel, Robert A Bray
As the practice of medicine becomes more reliant on imaging and laboratory tests, medical decisions will be increasingly based on numbers. Accordingly, following the introduction of solid-phase testing to the HLA testing repertoire, laboratory directors and physicians have employed preset mean fluorescence intensity (MFI) thresholds as the basis for decisions in the management of transplant patients. However, what do MFI values mean? The literature is rife with reports detailing numerous factors that influence antibody assessment including (but not limited to) sensitization history of the patient, level of mismatch between donor and recipient, presence of interfering substances in the serum, whether the antigen on multiplex beads is native or denatured, day-to-day and technologist variability, and the historical performance of an assay in a given institution...
May 30, 2017: Human Immunology
https://www.readbyqxmd.com/read/28576438/increase-of-allosensitization-after-a-kidney-graft-failure-predictors-and-effect-on-retransplantation-outcomes
#16
Andreia Campos, Jorge Malheiro, Sandra Tafulo, Sofia Santos, Leonídeo Dias, La Salete Martins, Manuela Almeida, Sofia Pedroso, A Castro Henriques, António Cabrita
Patients who are candidates for a second kidney transplant (SKT) frequently have a higher level of panel reactive antibodies (PRA). We assessed the allosensitisation change after a first graft failure (GF), its predictors and impact on retransplantat outcomes. We retrospectively selected 140 adult patients who received a SKT. Recipient and donor characteristics were analyzed. We defined the delta PRA (dPRA) as the difference between peak PRA before the SKT and first one (cohort median value=+10%). Logistic regression analysis was used to determine risk factors for dPRA≥10% and acute rejection (AR) in the SKT...
May 30, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28572563/effect-of-recipient-age-at-liver-transplantation-on-prevalence-of-post-transplant-donor-specific-hla-antibody
#17
Kazuaki Tokodai, Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Wataru Nakanishi, Michiaki Unno, Takashi Kamei
BACKGROUND Post-transplant donor-specific HLA antibodies (DSA) may have a detrimental effect on long-term outcomes of organ transplantation. The aim of this study was to specifically evaluate the effect of recipient age on the prevalence of DSA over a long-term follow-up after living donor liver transplantation (LDLT). MATERIAL AND METHODS A retrospective analysis of DSA evaluations was performed in 50 pediatric patients with HLA data available. Patients were divided into 2 groups based on their age at the time of LDLT: younger (Y) group, age <3 years; older (O) group, age ≥3 years...
June 2, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28571148/de-novo-focal-segmental-glomerulosclerosis-in-renal-allograft-histological-presentation-and-clinical-correlation-single-centre-experience
#18
Rashmi D Patel, Aruna V Vanikar, Lovelesh A Nigam, Kamal V Kanodia, Kamlesh S Suthar, Himanshu V Patel
INTRODUCTION: Recurrent or de novo glomerulonephritis are one of the well-known causes for renal allograft dysfunction in early and late period after renal transplantation. Focal Segmental Glomerulosclerosis (FSGS) is a devastating lesion of the renal allograft. De novo FSGS is uncommon compared to recurrent FSGS. AIM: To find out the incidence of de novo FSGS. MATERIALS AND METHODS: A retrospective evaluation of renal allograft biopsies was performed from 2007 to 2015, by light microscopy and immunohistochemistry including patient-donor demographics...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28557957/plasma-exosomes-from-hla-sensitized-kidney-transplant-recipients-contain-mrna-transcripts-which-predict-development-of-antibody-mediated-rejection
#19
Hao Zhang, Edmund Huang, Joseph Kahwaji, Cynthia C Nast, Ping Li, James Mirocha, David L Thomas, Shili Ge, Ashley A Vo, Stanley C Jordan, Mieko Toyoda
BACKGROUND: Sensitization to human leukocyte antigens (HLA) remains a significant immunologic barrier to successful transplantation. Identifying immune mechanisms responsible for antibody-mediated rejection (ABMR) is an important goal. Here we explored the possibility of predicting the risk for ABMR by measuring mRNA transcripts of ABMR-associated genes in plasma exosomes from kidney transplant patients. METHODS: Total RNA was extracted from exosomes purified from 152 EDTA-plasma samples of 64 patients (18 ABMR, 8 cell-mediated rejection [CMR], 38 no rejection in desensitized (DES) and non-desensitized (non-DES) control groups) for reverse transcription into cDNA, preamplification and then real time quantitative polymerase chain reaction (qPCR) for 21 candidate genes...
May 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28554738/circulating-donor-specific-anti-hla-antibodies-are%C3%A2-a%C3%A2-major-factor-in-premature-and-accelerated-allograft-fibrosis
#20
Clément Gosset, Denis Viglietti, Marion Rabant, Jérôme Vérine, Olivier Aubert, Denis Glotz, Christophe Legendre, Jean-Luc Taupin, Jean-Paul Duong Van-Huyen, Alexandre Loupy, Carmen Lefaucheur
Addressing the causes of kidney allograft-accelerated aging is an important challenge for improving long-term transplant outcomes. Here we investigated the role of circulating donor-specific anti-HLA antibodies (HLA-DSAs) in the development and the progression of kidney allograft fibrosis with inclusion of traditional risk factors for allograft fibrosis. We prospectively enrolled 1539 consecutive kidney recipients transplanted in two centers and assessed interstitial fibrosis and tubular atrophy (IF/TA) in biopsies performed at one year post-transplantation...
May 26, 2017: Kidney International
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