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https://www.readbyqxmd.com/read/28805293/utility-of-protocol-kidney-biopsies-for-de-novo-donor-specific-antibodies
#1
Sandesh Parajuli, Patrick K Reville, Thomas M Ellis, Arjang Djamali, Didier A Mandelbrot
There is limited information about the role of protocol kidney biopsies for de novo donor specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine post-transplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 that underwent kidney biopsy within 60 days of detection of dnDSA. 29 (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection...
August 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28776960/role-of-de-novo-donor-specific-anti-hla-antibodies-in-kidney-graft-failure-a-case-control-study
#2
Ana Castro, Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
The role of de novo donor-specific anti-HLA antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002-2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy...
August 4, 2017: HLA
https://www.readbyqxmd.com/read/28729289/class-ii-eplet-mismatch-modulates-tacrolimus-trough-levels-required-to-prevent-donor-specific-antibody-development
#3
Chris Wiebe, David N Rush, Thomas E Nevins, Patricia E Birk, Tom Blydt-Hansen, Ian W Gibson, Aviva Goldberg, Julie Ho, Martin Karpinski, Denise Pochinco, Atul Sharma, Leroy Storsley, Arthur J Matas, Peter W Nickerson
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch...
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28658512/early-clearance-vs-persistence-of-de-novo-donor-specific-antibodies-following-lung-transplantation
#4
Ana K Islam, Neeraj Sinha, Jennifer M DeVos, Thomas S Kaleekal, Soma S Jyothula, Larry D Teeter, Duc T M Nguyen, Todd N Eagar, Linda W Moore, Mamta Puppala, Stephen T C Wong, Richard J Knight, Adaani E Frost, Edward A Graviss, A Osama Gaber
BACKGROUND: The natural history of de novo donor-specific antibodies (dnDSA) after lung transplantation is not well-described. We sought to determine the incidence and risk factors associated with dnDSA and compare outcomes between recipients with transient (or isolated) vs persistent dnDSA after transplantation. METHODS: A single-center review of all lung transplants from 1/2009-7/2013. DSAs were tested eight times in the first year and every 4 months thereafter...
June 28, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28654684/intravenous-immunoglobulin-therapy-in-kidney-transplant-recipients-with-de-novo-dsa-results-of-an-observational-study
#5
Marie Matignon, Caroline Pilon, Morgane Commereuc, Cynthia Grondin, Claire Leibler, Tomek Kofman, Vincent Audard, José Cohen, Florence Canoui-Poitrine, Philippe Grimbert
BACKGROUND: Approximately 25% of kidney transplant recipients develop de novo anti-HLA donor-specific antibodies (dnDSA) leading to acute antibody-mediated rejection (ABMR) in 30% of patients. Preemptive therapeutic strategies are not available. METHODS: We conducted a prospective observational study including 11 kidney transplant recipients. Inclusion criteria were dnDSA occurring within the first year after transplant and normal allograft biopsy. All patients were treated with high-dose IVIG (2 g/kg 0, 1 and 2 months post-dnDSA)...
2017: PloS One
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
#6
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/28582797/the-detrimental-impact-of-persistent-vs-an-isolated-occurrence-of-de-novo-donor-specific-antibodies-on-intermediate-term-renal-transplant-outcomes
#7
Jennifer M Loucks-DeVos, Todd N Eagar, A Osama Gaber, Samir J Patel, Larry D Teeter, Edward A Graviss, Richard J Knight
BACKGROUND: De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. METHODS: A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA...
June 5, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28542109/application-and-interpretation-of-histocompatibility-data-in-pediatric-kidney-transplantation
#8
Hilda E Fernandez
PURPOSE OF REVIEW: Advances in technology to assess immunologic risk in solid organ transplant offer an opportunity to optimize the approach to pediatric deceased donor kidney transplant in the setting of a new allocation system in the United States. RECENT FINDINGS: Degree of human leukocyte antigen (HLA) mismatch, class II HLA mismatch, unacceptable antigens and donor-specific antibody (DSA) detected by solid-phase assays, and epitope matching pretransplant affect pediatric kidney transplant outcomes...
August 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28445619/mtor-inhibitors-and-risk-of-chronic-antibody-mediated-rejection-after-kidney-transplantation-where-are-we-now
#9
REVIEW
Philippe Grimbert, Olivier Thaunat
Antibody-mediated rejection (AMR) usually starts with generation of donor-specific anti-HLA antibodies (DSAs), arising from a B-cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling pathway involved in AMR-related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo. In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dnDSA) or AMR-regardless of the type of regimen-is patient adherence...
July 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28367453/de-novo-donor-specific-hla-antibodies-developing-early-or-late-after-transplant-are-associated-with-the-same-risk-of-graft-damage-and-loss-in-nonsensitized-kidney-recipients
#10
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago, Antonella Gurrado, Ilaria Guido, Francesca Compagno, Giacomo Garibotto, Catherine Klersy, Enrico Verrina, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, Fabrizio Ginevri
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28211192/racial-differences-in-incident-de-novo-donor-specific-anti-hla-antibody-among-primary-renal-allograft-recipients-results-from-a-single-center-cohort-study
#11
Matthew J Everly, Kimberly P Briley, Carl E Haisch, Georg Dieplinger, Paul Bolin, Scott A Kendrick, Claire Morgan, Angela Q Maldonado, Lorita M Rebellato
Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor-specific anti-human leucocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA-mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre- and post-transplant and tested for anti-HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non-AA), 107 developed dnDSA at a median of 9...
February 17, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28186642/higher-calcineurin-inhibitor-levels-predict-better-kidney-graft-survival-in-patients-with-de-novo-donor-specific-anti-hla-antibodies-a-cohort-study
#12
Marc-Antoine Béland, Isabelle Lapointe, Réal Noël, Isabelle Côté, Eric Wagner, Julie Riopel, Eva Latulippe, Olivier Désy, Stéphanie Béland, Ciara N Magee, Isabelle Houde, Sacha A De Serres
The development of de novo anti-HLA donor-specific antibodies (dnDSA) is associated with poorer outcomes in kidney transplant recipients. Despite this, antibody screening post-transplant is not widespread, largely because the optimal management of patients with dnDSA remains undetermined. We hypothesized that in this population, calcineurin inhibitor blood levels would be an independent predictor of graft loss. We analyzed a cohort of unsensitized patients for whom anti-HLA antibody screening was performed prospectively post-transplant...
February 10, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28181305/de-novo-dq-donor-specific-antibodies-are-associated-with-worse-outcomes-compared-to-non-dq-de-novo-donor-specific-antibodies-following-heart-transplantation
#13
Robert Townsend Cole, Jonathan Gandhi, Robert A Bray, Howard M Gebel, Alanna Morris, Andrew McCue, Michael Yin, S Raja Laskar, Wendy Book, Maan Jokhadar, Andrew Smith, Duc Nguyen, J David Vega, Divya Gupta
BACKGROUND: Antibody-mediated rejection (AMR) resulting from de novo donor-specific antibodies (dnDSA) leads to adverse outcomes following heart transplantation (HTx). It remains unclear what role dnDSA to specific HLA antigens play in adverse outcomes. This study compares outcomes in patients developing dnDSA to DQ antigens with those developing non-DQ dnDSA and those free from dnDSA. METHODS: The present study was a single-center, retrospective analysis of 122 consecutive HTx recipients...
April 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28104165/highly-immunogenic-dqb1-mismatch-eplets-are-associated-with-development-of-chronic-active-antibody-mediated-rejection-a-first-report-from-japan
#14
D Iwami, K Hotta, H Sasaki, T Hirose, H Higuchi, Y Takada, N Shinohara
BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/27989013/relationship-among-viremia-viral-infection-alloimmunity-and-nutritional-parameters-in-the-first-year-after-pediatric-kidney-transplantation
#15
R Ettenger, H Chin, K Kesler, N Bridges, P Grimm, E F Reed, M Sarwal, R Sibley, E Tsai, B Warshaw, A D Kirk
The Immune Development in Pediatric Transplantation (IMPACT) study was conducted to evaluate relationships among alloimmunity, protective immunity, immune development, physical parameters, and clinical outcome in children undergoing kidney transplantation. We prospectively evaluated biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA) formation, viremia, viral infection, T cell immunophenotyping, and body mass index (BMI)/weight Z scores in the first year posttransplantation in 106 pediatric kidney transplant recipients...
June 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27977905/the-value-of-protocol-biopsies-to-identify-patients-with-de-novo-donor-specific-antibody-at-high-risk-for-allograft-loss
#16
C A Schinstock, F Cosio, W Cheungpasitporn, D M Dadhania, M J Everly, M D Samaniego-Picota, L Cornell, M D Stegall
De novo donor-specific antibody (dnDSA) is associated with antibody-mediated rejection (AMR) and allograft loss, yet the allograft histology associated with dnDSA remains unclear. The aim of this study was to examine the allograft histology associated with dnDSA in patients with serial surveillance biopsies. We retrospectively studied adult conventional solitary kidney transplant recipients from October 2007 to May 2014. The definition of dnDSA was new donor-specific antibody (DSA) with mean fluorescence intensity (MFI) >1000...
June 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27888555/renal-operational-tolerance-is-associated-with-a-defect-of-blood-tfh-cells-that-exhibit-impaired-b-cell-help
#17
A Chenouard, M Chesneau, L Bui Nguyen, S Le Bot, M Cadoux, E Dugast, C Paul, S Malard-Castagnet, S Ville, P Guérif, J-P Soulillou, N Degauque, R Danger, M Giral, S Brouard
Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper (Tfh) cells play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene expression profile, failed to produce interleukin-21, and were unable to induce IgG production by naive B cells...
June 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27539748/evaluation-of-c1q-status-and-titer-of-de-novo-donor-specific-antibodies-as-predictors-of-allograft-survival
#18
C Wiebe, A J Gareau, D Pochinco, I W Gibson, J Ho, P E Birk, T Blydt-Hansen, M Karpinski, A Goldberg, L Storsley, D N Rush, P W Nickerson
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0...
March 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27501275/kidney-intragraft-homing-of-de-novo-donor-specific-hla-antibodies-is-an-essential-step-of-antibody-mediated-damage-but-not-per-se-predictive-of-graft-loss
#19
A Nocera, A Tagliamacco, M Cioni, A Innocente, I Fontana, G Barbano, A Carrea, M Ramondetta, A Sementa, S Basso, G Quartuccio, C Klersy, M Bertocchi, E Verrina, G Garibotto, G M Ghiggeri, M Cardillo, P Comoli, F Ginevri
Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens...
March 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27448994/donor-selection-in-pediatric-kidney-transplantation-using-dr-and-dq-eplet-mismatching-a-new-histocompatibility-paradigm
#20
Christopher F Bryan, Vimal Chadha, Bradley A Warady
It is now appreciated that more HLA-DR mismatching at the time of the first renal transplant is associated with higher degrees of sensitization, lower rates and longer times to retransplantation, and worse graft outcomes in children who are subsequently retransplanted. As such, our pediatric renal transplant program preferentially uses 0 or 1 HLA-DR-mismatched kidneys and reserves 2 DR-mismatched kidneys for recipients with an eminent need for a kidney. Based on a new HLA class II epitope matching strategy that is designed to minimize dnDSA production to DR and DQ antigens, we evaluated the prevalence of DR and DQ eplet mismatching for dd offers made to our pediatric wait-listed candidates...
November 2016: Pediatric Transplantation
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