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transplantating in low level DSA

J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (CTLA4Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor specific antibodies (DSA) make it an interesting agent in hand transplantation. In order to reduce CNI immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand transplanted patients at month 4, at 6, 9, and 13 years after hand/forearm transplantation. Patients received 5mg/kg belatacept every 2 weeks, the dosing interval was extended to 4 weeks after 5 applications...
July 25, 2017: American Journal of Transplantation
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
Olivier Aubert, Alexandre Loupy, Luis Hidalgo, Jean-Paul Duong van Huyen, Sarah Higgins, Denis Viglietti, Xavier Jouven, Denis Glotz, Christophe Legendre, Carmen Lefaucheur, Philip F Halloran
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205)...
June 2017: Journal of the American Society of Nephrology: JASN
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell-depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
May 2017: Transplantation
Carrie Schinstock, Manish Gandhi, Wisit Cheungpasitporn, Donald Mitema, Mikel Prieto, Patrick Dean, Lynn Cornell, Fernando Cosio, Mark Stegall
BACKGROUND: Avoiding donor specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed. METHODS: We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low+XM, +DSA/high+XM, and -DSA/+XM and followed for a mean of 4.1±1...
December 22, 2016: Transplantation
J Kanter Berga, A Sancho Calabuig, E Gavela Martinez, N Puig Alcaraz, A Avila Bernabeu, J Crespo Albiach, P Molina Vila, S Beltrán Catalan, L Pallardó Mateu
BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients...
November 2016: Transplantation Proceedings
Benjamin Chaigne, Kirsten Geneugelijk, Benot Bdat, Mohamed Alibashe Ahmed, Gideon Hnger, Sophie de Seigneux, Sandrine Demuylder-Mischler, Thierry Berney, Eric Spierings, Sylvie Ferrari-Lacraz, Jean Villard
The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant...
November 2016: Cell Transplantation
Wannarat Pongpirul, Wiwat Chancharoenthana, Krit Pongpirul, Asada Leelahavanichakul, Wipawee Kittikowit, Kamonwan Jutivorakool, Bunthoon Nonthasoot, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa, Natavudh Townamchai
BACKGROUND: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection...
November 26, 2016: Nephrology
David Shaffer, Irene D Feurer, Deborah Crowe, Heidi Schaefer
BACKGROUND: Desensitization with IVIG and rituximab allows acceptable graft survival in sensitized kidney transplant recipients with preexisting donor-specific antibodies (DSAs) and a positive crossmatch. There is little published data reporting the durability of DSA removal in kidney transplant recipients treated with IVIG and rituximab. METHODS: We conducted a 3-year prospective DSA monitoring study in living donor kidney recipients with preexisting DSA to assess the durability of DSA removal after a perioperative protocol of IVIG and rituximab...
February 2016: Transplantation Direct
Vadim Jucaud, Mepur H Ravindranath, Paul I Terasaki
BACKGROUND: Single antigen beads (SAB) are used for monitoring HLA antibodies in pretransplant and posttransplant patients despite the discrepancy between virtual and actual crossmatch results and transplant outcomes. This discrepancy can be attributed to the presence of conformational variants of HLA-I on SAB, assessment of which would increase the concordance between SAB and flow cytometry crossmatch (FCXM) results, thus enabling improved organ accessibility for the waiting list patients and a better prediction of antibody-mediated rejection...
April 2017: Transplantation
Benjamin Chaigne, Kirsten Geneugelijk, Benoît Bédat, Mohamed Alibashe Ahmed, Gideon Hönger, Sophie de Seigneux, Sandrine Demuylder-Mischler, Thierry Berney, Eric Spierings, Sylvie Ferrari-Lacraz, Jean Villard
The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity and anti-HLA antibody characteristic were collected. Between January 2008 and July 2014, 18 patients received islet transplants and 26 patients received a pancreas transplant...
May 18, 2016: Cell Transplantation
Yan Zhang, David Briggs, David Lowe, Daniel Mitchell, Sunil Daga, Nithya Krishnan, Robert Higgins, Natasha Khovanova
The dynamics of donor specific human leukocyte antigen antibodies during early stage after kidney transplantation are of great clinical interest as these antibodies are considered to be associated with short and long term clinical outcomes. The limited number of antibody time series and their diverse patterns have made the task of modelling difficult. Focusing on one typical post-transplant dynamic pattern with rapid falls and stable settling levels, a novel data-driven model has been developed for the first time...
May 14, 2016: Mathematical Biosciences
L J Ceulemans, F Braza, D Monbaliu, I Jochmans, G De Hertogh, J Du Plessis, M-P Emonds, H Kitade, M Kawai, Y Li, X Zhao, T Koshiba, B Sprangers, S Brouard, M Waer, J Pirenne
Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation...
October 2016: American Journal of Transplantation
Kwanchai Pirojsakul, Dev Desai, Chantale Lacelle, Mouin G Seikaly
BACKGROUND: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. METHODS: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %...
October 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Antonio Cuadrado, David San Segundo, Marcos López-Hoyos, Javier Crespo, Emilio Fábrega
Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported...
October 21, 2015: World Journal of Gastroenterology: WJG
Arnaud Del Bello, Nicolas Congy-Jolivet, Marie Danjoux, Fabrice Muscari, Laurence Lavayssière, Laure Esposito, Isabelle Cardeau-Desangles, Joëlle Guitard, Gaëlle Dörr, David Milongo, Bertrand Suc, Jean Pierre Duffas, Laurent Alric, Christophe Bureau, Céline Guilbeau-Frugier, Lionel Rostaing, Nassim Kamar
The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1...
December 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
Farsad Eskandary, Gregor Bond, Heinz Regele, Nicolas Kozakowski, Zeljko Kikić, Markus Wahrmann, Helmuth Haslacher, Rainer Oberbauer, Vido Ramassar, Philip Halloran, Georg A Böhmig
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; 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...
2014: Clinical Transplants
Natasha Khovanova, Sunil Daga, Torgyn Shaikhina, Nithya Krishnan, James Jones, Daniel Zehnder, Daniel Mitchell, Robert Higgins, David Briggs, David Lowe
Donor HLA-specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan-IgG level and at 30 days post-transplantation in eighty HLA antibody-incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody-mediated rejection (P = 0...
December 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
Georg A Böhmig, Zeljko Kikic, Markus Wahrmann, Farsad Eskandary, Arezu Z Aliabadi, Gerhard J Zlabinger, Heinz Regele, Helmut E Feucht
OBJECTIVE: Antibody-mediated rejection (ABMR) is an important cause of kidney allograft injury. In the last two decades, detection of complement split product C4d along transplant capillaries, a footprint of antibody-mediated classical complement activation, has evolved as a useful diagnostic marker of ABMR. While it was recognized that ABMR may occur also in the absence of C4d, numerous studies have shown that C4d deposition may indicate a more severe rejection phenotype associated with poor graft survival...
March 2016: Clinical Biochemistry
Rob Higgins, David Lowe, Sunil Daga, Mark Hathaway, C Williams, F T Lam, Habib Kashi, Lam Chin Tan, Chris Imray, Simon Fletcher, Nithya Krishnan, Pat Hart, Daniel Zehnder, David Briggs
Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870)...
August 2015: Human Immunology
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