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https://www.readbyqxmd.com/read/29452978/the-management-of-antibodies-in-heart-transplantation-an-ishlt-consensus-document
#1
Jon Kobashigawa, Monica Colvin, Luciano Potena, Duska Dragun, Maria G Crespo-Leiro, Juan F Delgado, Michael Olymbios, Jayan Parameshwar, Jignesh Patel, Elaine Reed, Nancy Reinsmoen, E Rene Rodriguez, Heather Ross, Randall C Starling, Dolly Tyan, Simon Urschel, Andreas Zuckermann
Despite the successes from refined peri-operative management techniques and immunosuppressive therapies, antibodies remain a serious cause of morbidity and mortality for patients both before and after heart transplantation. Patients awaiting transplant who possess antibodies against human leukocyte antigen are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory support devices...
January 31, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29451342/deleterious-effect-of-anti-angiotensin-ii-type-1-receptor-antibodies-detected-pretransplant-on-kidney-graft-outcomes-is-both-proper-and-synergistic-with-donor-specific-anti-hla-antibodies
#2
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
AIM: Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs with or without concomitant DSA on KT outcomes. METHODS: Seventy-six patients transplanted in 2009 were studied. DSA (MFI>1000) and/or AT1R-abs (>10UI) were detected by solid-phase assays in pre-KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure...
February 16, 2018: Nephrology
https://www.readbyqxmd.com/read/29446208/study-rationale-design-and-pre-transplant-alloantibody-status-a-first-report-of-clinical-trials-in-organ-transplantation-in-children-04-ctotc-04-in-pediatric-heart-transplantation
#3
Warren A Zuckerman, Adriana Zeevi, Kristen L Mason, Brian Feingold, Carol Bentlejewski, Linda J Addonizio, Elizabeth D Blume, Charles E Canter, Anne I Dipchand, Daphne T Hsu, Robert E Shaddy, William T Mahle, Anthony J Demetris, David M Briscoe, Thalachallour Mohanakumar, Joseph M Ahearn, David N Iklé, Brian D Armstrong, Yvonne Morrison, Helena Diop, Jonah Odim, Steven A Webber
Anti-HLA donor-specific antibodies are associated with worse outcomes following organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase post-transplant morbidity and mortality. We address this clinical challenge in a prospective, multi-center, observational cohort study of children listed for heart transplantation (CTOTC-04). Outcomes were compared among sensitized recipients who underwent transplant with positive crossmatch, non-sensitized recipients, and sensitized recipients without positive crossmatch...
February 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29444290/impact-of-renal-allograft-nephrectomy-on-graft-and-patient-survival-following-retransplantation-a-systematic-review-and-meta-analysis
#4
Jinwen Lin, Rending Wang, Ying Xu, Jianghua Chen
Background: It is not clear whether renal allograft removal affects the outcome of renal retransplantation. This study aimed to determine the effect of allograft nephrectomy (AN) and no-AN (No AN) on renal retransplantation. Methods: A systematic review and meta-analysis were conducted using MEDLINE, Embase and the Cochrane Library. Observational studies or randomized controlled trials including renal retransplantation recipients with AN or No-AN were included. The primary outcomes were graft survival, patient survival, acute rejection (AR) and delayed graft dysfunction; the secondary outcomes were positive panel reactive antibody rate and serum creatinine level at 1 year after retransplantation, cold ischemia time and time of hemodialysis before recent transplantation...
February 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29444269/association-of-angiotensin-ii-type-1-receptor-antibodies-with-graft-histology-function-and-survival-in-paediatric-renal-transplant-recipients
#5
Alexander Fichtner, Caner Süsal, Claudia Schröder, Britta Höcker, Susanne Rieger, Rüdiger Waldherr, Jens H Westhoff, Anja Sander, Duska Dragun, Burkhard Tönshoff
Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology...
February 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29443827/a-comparison-of-hla-molecular-mismatch-methods-to-determine-hla-immunogenicity
#6
C Wiebe, V Kosmoliaptsis, D Pochinco, C Taylor, P Nickerson
BACKGROUND: Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level, however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression. METHODS: HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development...
February 13, 2018: Transplantation
https://www.readbyqxmd.com/read/29442424/incidence-characterization-and-impact-of-newly-detected-donor-specific-anti-hla-antibody-in-the-first-year-after-pediatric-heart-transplantation-a-report-from-the-ctotc-04-study
#7
A I Dipchand, S Webber, K Mason, B Feingold, C Bentlejewski, W T Mahle, R Shaddy, C Canter, E D Blume, J Lamour, W Zuckerman, H Diop, Y Morrison, B Armstrong, D Ikle, J Odim, A Zeevi
Data on the clinical importance of newly detected donor specific antibodies (ndDSA) following pediatric heart transplantation is lacking despite mounting evidence of the detrimental effect of de novo DSA in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSA in the first year post-transplant in order to determine their incidence, pattern and clinical impact. One third of patients developed ndDSA; when present, these were mostly detected within the first 6 weeks after transplant suggesting that memory responses may predominate over true de novo DSA production in this population...
February 14, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29428484/pre-transplant-screening-for-non-hla-antibodies-who-should-be-tested
#8
Mary Carmelle Philogene, Sheng Zhou, Bonnie E Lonze, Serena Bagnasco, Sami Alasfar, Robert A Montgomery, Edward Kraus, Annette M Jackson, Mary S Leffell, Andrea A Zachary
Retrospective studies of angiotensin II type 1 receptor antibodies (AT1R-Ab) and anti-endothelial cell antibodies (AECA) have linked these antibodies to allograft injury. Because rising healthcare costs dictate judicious use of laboratory testing, we sought to define characteristics of kidney transplant recipients who may benefit from screening for non-HLA antibodies. Kidney recipients transplanted between 2011 and 2016 at Johns Hopkins, were evaluated for AT1R-Ab and AECA. Pre-transplant antibody levels were compared to clinical and biopsy indications of graft dysfunction...
February 8, 2018: Human Immunology
https://www.readbyqxmd.com/read/29407335/late-steroid-withdrawal-following-ab0-incompatible-renal-transplantation
#9
F Bachmann, N Lachmann, K Budde, L Liefeldt, F Halleck, M Naik, F Friedersdorff, B Rudolph, K Wu, O Meyer, T Slowinski, J Waiser
BACKGROUND: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29407292/impact-of-interleukin-17f-gene-polymorphisms-in-outcome-of-kidney-transplantation-in-tunisian-recipients
#10
Y Haouami, I Sfar, T Dhaouadi, T Gargah, M Bacha, R Bardi, E Abderrahim, R Goucha, M Ounissi, T Ben Abdallah, Y Gorgi
BACKGROUND: Genetic polymorphisms of interleukin (IL)-17F, associated with functional and/or quantitative change in this glycoprotein, have been described as predisposing to various autoimmune diseases. The proinflammatory IL-17 has some roles in renal transplantation. In this context, the relationship between the most common IL-17F polymorphisms with acute renal allograft rejection susceptibility in Tunisian renal recipients has been investigated. METHODS: We examined 93 renal transplant recipients who were enrolled and classified as follows: GI, 48 transplant recipients who developed at least one episode of acute rejection; and GII, 45 controls, kidney recipients who also were followed for at least 1 year and had stable renal function...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29405445/the-possible-critical-role-of-t-cell-help-in-dsa-mediated-graft-loss
#11
REVIEW
Caner Süsal, Antonij Slavcev, Lien Pham, Martin Zeier, Christian Morath
In the present review, we discuss a possible central role of T cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect...
February 6, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29369525/biologic-mechanisms-and-clinical-consequences-of-pregnancy-alloimmunization
#12
Paige M Porrett
Alloimmunization occurs during pregnancy when tissue antigens derived from the fetus and/or placenta prime maternal immune cells to divide and differentiate. For many women, the result of pregnancy alloimmunization is the formation of anti-HLA antibody that can endure for decades and preclude transplantation by limiting donor compatibility. Pregnancy alloimmunization may also generate memory B cells that can rapidly produce anti-HLA antibody after transplantation as well as pathogenic memory T cells which pose a threat to graft survival...
January 25, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29363222/obliterative-portal-venopathy-a-histopathologic-finding-associated-with-chronic-antibody-mediated-rejection-in-pediatric-liver-allografts
#13
Marjorie-Anne R Guerra, Bita V Naini, Jason V Scapa, Elaine F Reed, Ronald W Busuttil, Elaine Y Cheng, Douglas G Farmer, Jorge H Vargas, Robert S Venick, Sue V McDiarmid, Laura J Wozniak
The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV...
January 24, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29359404/heterogeneity-of-memory-b-cells
#14
REVIEW
Anita S Chong, M Javeed Ansari
Potential solid organ transplant recipients broadly sensitized to HLA have long wait times, low transplant rates and poor outcomes. The new kidney allocation system has improved access to the most highly sensitized recipients; however, their long-term outcomes are unknown. Emerging data suggest that memory B cell repertoire is broader than the plasma cell repertoire, therefore, despite refinements in anti-HLA antibody detection technology, donor-specific HLA- specific memory B cells may in fact be present in some, if not most, highly sensitized recipients with no detectable donor-specific antibodies...
January 23, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29358179/strategies-to-activate-nk-cells-to-prevent-relapse-and-induce-remission-following-hematopoietic-stem-cell-transplantation
#15
Sarah Cooley, Peter Parham, Jeffrey S Miller
Natural Killer (NK) cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. After allogeneic transplantation, NK cells are the first reconstituting lymphocytes, but are dysfunctional. Manipulating this first wave of lymphocytes could be instrumental in reducing the 40% relapse rate following transplantation with reduced intensity conditioning. NK cells express numerous activating and inhibitory receptors. Some recognize classical or non-classical HLA class I ligands, others recognize class I-like ligands or unrelated ligands...
January 22, 2018: Blood
https://www.readbyqxmd.com/read/29356221/results-of-early-treatment-for-de-novo-donor-specific-antibodies-in-pediatric-kidney-transplant-recipients-in-a-cross-sectional-and-longitudinal-cohort
#16
Olga Charnaya, Shamir Tuchman, Asha Moudgil
The development of dnDSA anti-HLA antibodies has been shown to be a significant risk factor for graft failure. In 2008, we instituted a routine protocol of standardized monitoring and treatment of dnDSA in pediatric kidney transplant recipients. Of 67 first-time pediatric kidney transplant recipients, 26 (38%) developed dnDSA after 1.36 (IQ 1-2.14) years. Coefficient of variance of tacrolimus, a surrogate marker of non-adherence, was found to be the single most important risk factor for dnDSA development. Overall, there was a significant reduction in dnDSA with treatment in 19 (76%) children...
January 22, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29343892/first-two-bilateral-hand-transplantations-in-india-part-4-immediate-post-operative-care-immunosuppression-protocol-and-monitoring
#17
Subramania Iyer, Mohit Sharma, P Kishore, Jimmy Mathew, R Janarthanan, Raghuveer Reddy, Abhijeet Wakure, Sundeep Vijayaraghavan, S M Chetan Mali, Visakh Varma, Ashish Chaudhari, Swapnil Dhake, Akshay Omkumar, George Kurian, Rajesh Nair, Anil Mathew, Zachariah Paul, Malini Eapen, Lalitha Biswas
Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC)...
May 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
https://www.readbyqxmd.com/read/29342289/recent-advances-in-kidney-transplantation-a-viewpoint-from-the-descartes-advisory-board
#18
Daniel Abramowicz, Rainer Oberbauer, Uwe Heemann, Ondrej Viklicky, Licia Peruzzi, Christophe Mariat, Marta Crespo, Klemens Budde, Gabriel C Oniscu
Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation...
January 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29335625/the-european-society-for-blood-and-marrow-transplantation-ebmt-consensus-guidelines-for-the-detection-and-treatment-of-donor-specific-anti-hla-antibodies-dsa-in-haploidentical-hematopoietic-cell-transplantation
#19
REVIEW
Stefan O Ciurea, Kai Cao, Marcelo Fernadez-Vina, Piyanuch Kongtim, Monzr Al Malki, Ephraim Fuchs, Leo Luznik, Xiao-Jun Huang, Fabio Ciceri, Franco Locatelli, Franco Aversa, Luca Castagna, Andrea Bacigalupo, Massimo Martelli, Didier Blaise, Rupert Handgretinger, Denis-Claude Roy, Paul O'Donnell, Asad Bashey, Hillard M Lazarus, Karen Ballen, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29331505/successful-treatment-of-anti-angiotensin-ii-type-1-receptor-antibody-associated-rejection-in-kidney-transplantation-a-case-report
#20
P Wiwattanathum, A Ingsathit, D Thammanichanond, S Worawichawong
Angiotensin II type 1 receptor (AT1R) antibody, a non-HLA antibody, has been found to have a detrimental effect on kidney allografts. Similarly to HLA antibodies, recipients who have AT1R antibodies are at risk for allograft rejection and poor long-term graft outcome. Besides mediating allograft rejections via direct effects on endothelial and vascular smooth muscle without complement activation, AT1R antibodies may lead to accelerated hypertension via the renin-angiotensin pathway. There has been no definite level of AT1R antibody that predicts allograft rejection...
January 10, 2018: Transplantation Proceedings
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