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https://www.readbyqxmd.com/read/27914702/renal-xenotransplantation-experimental-progress-and-clinical-prospects
#1
Martin Wijkstrom, Hayato Iwase, Wayne Paris, Hidetaka Hara, Mohamed Ezzelarab, David K C Cooper
There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27894836/use-of-complement-binding-assays-to-assess-the-efficacy-of-antibody-mediated-rejection-therapy-and-prediction-of-graft-survival-in-kidney-transplantation
#2
Daniel S Ramon, Yihung Huang, Lili Zhao, TrisAnn Rendulic, Jeong M Park, Randall S Sung, Milagros Samaniego
BACKGROUND: The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR...
November 25, 2016: Human Immunology
https://www.readbyqxmd.com/read/27870356/clinical-and-immunological-relevance-of-antibodies-in-solid-organ-transplantation
#3
REVIEW
N K Mehra, A K Baranwal
The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection...
December 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27830476/production-of-heterozygous-alpha-1-3-galactosyltransferase-ggta1-knock-out-transgenic-miniature-pigs-expressing-human-cd39
#4
Kimyung Choi, Joohyun Shim, Nayoung Ko, Heejong Eom, Jiho Kim, Jeong-Woong Lee, Dong-Il Jin, Hyunil Kim
Production of transgenic pigs for use as xenotransplant donors is a solution to the severe shortage of human organs for transplantation. The first barrier to successful xenotransplantation is hyperacute rejection, a rapid, massive humoral immune response directed against the pig carbohydrate GGTA1 epitope. Platelet activation, adherence, and clumping, all major features of thrombotic microangiopathy, are inevitable results of immune-mediated transplant rejection. Human CD39 rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator...
November 9, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27777772/urothelial-carcinoma-of-donor-origin-in-a-kidney-transplant-patient
#5
Rosa M Michel Ortega, Daynna J Wolff, Cynthia A Schandl, Harry A Drabkin
BACKGROUND: Malignancy after transplantation is an uncommon multifactorial occurrence. Immunosuppression to prevent graft rejection is described as a major risk factor in malignancy development in the post-transplant state. Donor-derived malignancy is a rare reported complication. Herein, we review our patient history and discuss diagnostic strategies and the implications of immunosuppression for donor-derived malignancy. CASE PRESENTATION: This is a 69-year-old man with post-renal-transplant urothelial carcinoma determined to be of donor origin...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27752765/acute-kidney-transplant-rejection-mediated-by-angiotensin-ii-type-1-receptor-antibodies-in-a-pediatric-hyperimmune-patient
#6
Isabella Guzzo, Federica Morolli, Francesca Diomedi Camassei, Antonina Piazza, Elvira Poggi, Luca Dello Strologo
BACKGROUND: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. CASE-DIAGNOSIS/TREATMENT: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d...
January 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27743177/pretransplantation-monitoring-of-hla-antibodies-by-complement-dependent-cytotoxicity-and-luminex-based-assays
#7
Nataša Katalinić, Marina Fućak, Tajana Crnić, Milena Ćurković, Alma Starčević, Sanja Balen
BACKGROUND: The introduction of more sensitive techniques, such as Luminex® for HLA antibody screening of patients awaiting organ transplantation has resulted in a better understanding of transplantation immunology and improvements in clinical practice. OBJECTIVE: The interpretation of the results obtained only by Luminex® can lead to inaccurate evaluation of a patient's antibody status and unjustified rejection of a potential organ donor. The aim of this study was to demonstrate the benefits of performing HLA antibody screening in the sera of patients on the waiting list for organ transplantation by two different assays, complement dependent cytotoxicity (CDC) and Luminex®...
October 14, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27742323/positive-rates-of-preliminary-crossmatches-among-transplantation-candidates-waitlisted-for-different-organs-in-the-korean-network-for-organ-sharing
#8
M H Park, S Kim, H Hwang, H Park, J Kwak, E K Kwon, H Y Sung, B Han
OBJECTIVE: For deceased-donor organ transplantations, negative T cell crossmatches (XMs) are mandatory for kidney and pancreas allocation in the Korean Network for Organ Sharing (KONOS) organ allocation system. Submission and periodic renewal of serum to the KONOS is required for all transplantation candidates of kidney or pancreas and these sera are distributed to 23 laboratories for preliminary XMs. We have investigated how sensitization status varies among transplantation candidates waitlisted for different organs...
September 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27742303/hyperacute-rejection-in-a-kidney-transplant-with-negative-crossmatch-a-case-report
#9
M Pereira, J Guerra, J Gonçalves, A Santana, C Nascimento, A G da Costa
Hyperacute rejection (HAR) is a rare event that can be prevented by crossmatch tests that detect anti-human leukocyte antigen antibodies against the donor. We present the case of a 43-year-old man who underwent a deceased-donor kidney transplantation with a negative complement-dependent cytotoxicity and a negative flow cytometry crossmatch. Luminex technology detected anti-DQ donor-specific antibodies (DSA) with a mean fluorescence intensity of 11,000. A single plasmapheresis session was carried out, followed by immunosuppression with immunoglobulin, antithymocyte globulin, tacrolimus, and methylprednisolone...
September 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27707997/mannan-binding-lectin-associated-serine-protease-1-3-cleavage-of-pro-factor-d-into-factor-d-in-vivo-and-attenuation-of-collagen-antibody-induced-arthritis-through-their-targeted-inhibition-by-rna-interference-mediated-gene-silencing
#10
Nirmal K Banda, Sumitra Acharya, Robert I Scheinman, Gaurav Mehta, Marilyne Coulombe, Minoru Takahashi, Hideharu Sekine, Steffen Thiel, Teizo Fujita, V Michael Holers
The complement system is proposed to play an important role in the pathogenesis of rheumatoid arthritis (RA). The complement system mannan-binding lectin-associated serine proteases (MASP)-1/3 cleave pro-factor D (proDf; inactive) into Df (active), but it is unknown where this cleavage occurs and whether inhibition of MASP-1/3 is a relevant therapeutic strategy for RA. In the present study, we show that the cleavage of proDf into Df by MASP-1/3 can occur in the circulation and that inhibition of MASP-1/3 by gene silencing is sufficient to ameliorate collagen Ab-induced arthritis in mice...
November 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27563301/antibody-dependent-nk-cell-activation-is-associated-with-late-kidney-allograft-dysfunction-and-the-complement-independent-alloreactive-potential-of-donor-specific-antibodies
#11
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27512839/analysis-of-4000-kidney-transplantations-in-a-single-center-across-immunological-barriers
#12
Hyunwook Kwon, Young Hoon Kim, Ji Yoon Choi, Shin Sung, Joo Hee Jung, Su-Kil Park, Duck Jong Han
Kidney transplant (KT) is the optimal renal replacement therapy for patients with end-stage renal disease (ESRD). The demand for kidneys, however, continues to exceed the supply. To overcome this problem, efforts to extend the donor pool by including human leukocyte antigen (HLA)- and ABO-incompatible (ABOi) KTs are increasing. The aim of this article was to retrospectively review data on recipients, donor profiles, and clinical outcomes in 4000 cases of KT. In addition, we analyzed clinical outcomes in ABOi and flow-cytometric crossmatch (FCXM) positive KT in a subgroup analysis...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27501352/eculizumab-therapy-for-chronic-antibody-mediated-injury-in-kidney-transplant-recipients-a-pilot-randomized-controlled-trial
#13
S Kulkarni, N C Kirkiles-Smith, Y H Deng, R N Formica, G Moeckel, V Broecker, L Bow, R Tomlin, J S Pober
We hypothesized that de novo donor-specific antibody (DSA) causes complement-dependent endothelial cell injury in kidney transplants, as assessed by expression of endothelial cell-associated transcripts (ENDATs), that may be attenuated through complement inhibition. In total, 15 participants (five control, 10 treatment) with DSA and deteriorating renal function were enrolled. The treatment group received 6 mo of eculizumab followed by 6 mo of observation, whereas controls were observed. The primary end point was percentage change in estimated GFR (eGFR) trajectory over the treatment period...
August 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27348472/evidence-for-an-important-role-of-both-complement-binding-and-noncomplement-binding-donor-specific-antibodies-in-renal-transplantation
#14
Denis Viglietti, Carmen Lefaucheur, Denis Glotz
PURPOSE OF REVIEW: The review describes the current clinical relevance of circulating anti-human leukocyte antigen (anti-HLA) antibodies in kidney transplantation and discusses recent improvements in their characterization that provide new insights into the identification and management of important clinical outcomes. RECENT FINDINGS: Recent studies addressing the relationships between donor-specific anti-HLA antibody (HLA-DSA) properties (i.e., their strength, complement-binding capacity, and IgG subclass composition) and allograft injury and survival have highlighted their relevance in the prediction of antibody-mediated injury and allograft loss...
August 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27258774/protein-a-immunoadsorption-may-hamper-the-decision-to-transplant-due-to-interference-with-cdc-crossmatch-results
#15
Pernille Koefoed-Nielsen, Claus Bistrup, Mette Christiansen
Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers...
June 3, 2016: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/27239362/false-positive-b-cells-crossmatch-after-prior-rituximab-exposure-of-the-kidney-donor
#16
Judith Desoutter, Marie-Joëlle Apithy, Ségolène Bartczak, Nicolas Guillaume
Crossmatching is essential prior to kidney transplantation to confirm compatibility between the donor and the recipient, particularly to prevent acute antibody-mediated rejection. An unexpected positive crossmatch may be obtained in recipients with an autoimmune disease or preexisting antibodies not detected by single-antigen bead array due to complement interference or who have been previously treated by desensitization protocols such as rituximab, antithymocyte globulin, or intravenous immunoglobulins. We report donor and recipient investigations that revealed unexpected positive B-cells crossmatch, probably due to donor cells, as the donor had received rituximab therapy shortly before organ harvesting, in a context of severe idiopathic thrombocytopenic purpura...
2016: Case Reports in Transplantation
https://www.readbyqxmd.com/read/27234729/role-of-pretransplant-complement-fixing-donor-specific-antibodies-identified-by-c1q-assay-in-kidney-transplantation
#17
D Thammanichanond, P Wiwattanathum, T Mongkolsuk, S Kantachuvesiri, S Worawichawong, S A Vallipakorn, P Kitpoka
BACKGROUND: Kidney transplant recipients who have pretransplant donor-specific human leukocyte antigen (HLA) antibodies have greater risk for developing allograft rejection and allograft loss. However, there is a varied effect of graft injury among patients with pretransplantation donor-specific antibodies (DSA). The difference of complement activating ability may be the reason why some DSA are detrimental to kidney allograft. This study aimed to investigate the association between pretransplantation C1q-binding DSA and clinical outcomes...
April 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27215234/c1q-binding-anti-hla-antibody-assay-a-test-dilemma
#18
EDITORIAL
Ali H Hajeer
Detection of donor-specific anti-HLA antibodies in patients with kidney graft, or awaiting kidney graft, acts as a predictor for antibody mediated rejection. Several methods are in practice for the detection of anti-HLA antibodies; including the latest introduction of C1q-binding anti-HLA antibody method. This method depends on detecting complement fixing anti-HLA antibodies on single antigen beads using C1q as the marker for the presence of those antibodies. Here we discuss recent data on this method and present a working hypothesis for explaining the inability of this method to detect low titer anti-HLA antibodies...
May 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27190362/deceased-donor-kidney-transplantation-across-donor-specific-antibody-barriers-predictors-of-antibody-mediated-rejection
#19
Elisabeth Schwaiger, Farsad Eskandary, Nicolas Kozakowski, Gregor Bond, Željko Kikić, Daniel Yoo, Susanne Rasoul-Rockenschaub, Rainer Oberbauer, Georg A Böhmig
BACKGROUND: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR). METHODS: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization...
August 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27120452/diagnostic-contribution-of-donor-specific-antibody-characteristics-to-uncover-late-silent-antibody-mediated-rejection-results-of-a-cross-sectional-screening-study
#20
Farsad Eskandary, Gregor Bond, Nicolas Kozakowski, Heinz Regele, Lena Marinova, Markus Wahrmann, Željko Kikić, Helmuth Haslacher, Susanne Rasoul-Rockenschaub, Christopher C Kaltenecker, Franz König, Luis G Hidalgo, Rainer Oberbauer, Philip F Halloran, Georg A Böhmig
BACKGROUND: Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR. METHODS: Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation...
April 26, 2016: Transplantation
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