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https://www.readbyqxmd.com/read/28211192/racial-differences-in-incident-de-novo-donor-specific-anti-hla-antibody-among-primary-renal-allograft-recipients
#1
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 leukocyte 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
#2
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-dndsa-following-heart-transplantation
#3
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: Single-center, retrospective analysis of 122 consecutive HTx recipients...
February 9, 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
#4
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
#5
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...
December 18, 2016: 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
#6
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...
December 15, 2016: 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
#7
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...
November 26, 2016: 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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27196395/disparate-rates-of-acute-rejection-and-donor-specific-antibodies-among-high-immunologic-risk-renal-transplant-subgroups-receiving-antithymocyte-globulin-induction
#11
Samir J Patel, Wadi N Suki, Jennifer Loucks-DeVos, Edward A Graviss, Duc T Nguyen, Richard J Knight, Samantha A Kuten, Linda W Moore, Larry D Teeter, Lillian W Gaber, A Osama Gaber
Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression...
August 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27163535/inflammation-in-early-kidney-allograft-surveillance-biopsies-with-and-without-associated-tubulointerstitial-chronic-damage-as-a-predictor-of-fibrosis-progression-and-development-of-de-novo-donor-specific-antibodies
#12
Clara García-Carro, Christina Dörje, Anders Åsberg, Karsten Midtvedt, Helge Scott, Finn P Reinholt, Hallvard Holdaas, Daniel Seron, Anna V Reisæter
BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) associated with interstitial inflammation in nonscarred areas (IFTA+i) is associated with poorer graft outcome than inflammation without IFTA or IFTA without inflammation. METHODS: We evaluated if histological categories at week 6 could predict the development of interstitial fibrosis and de novo donor specific anti-HLA antibodies (dnDSA) at 1 year. Biopsies were classified according to Banff criteria as normal (i+t≤1 and ci+ct≤1), inflammation (i+t≥2 and ci+ct≤1), IFTA (i+t≤1 and ci+ct≥2) or IFTA+i (i+t≥2 and ci+ct≥2)...
May 10, 2016: Transplantation
https://www.readbyqxmd.com/read/27106124/de-novo-donor-specific-human-leukocyte-antigen-antibody-screening-in-kidney-transplant-recipients-after-the-first-year-posttransplantation-a-medical-decision-analysis
#13
B A Kiberd, A Miller, S Martin, K K Tennankore
Screening for de novo donor-specific antibodies (dnDSA) in stable kidney transplant recipients is routine practice in some centers. Patients with DSA are at increased risk of graft loss and early intervention may improve outcomes. However, the costs and benefits of dnDSA surveillance are unknown. A medical decision analysis to examine a screening strategy was developed for kidney transplant recipients who had stable graft function and were DSA negative 1 year posttransplant. In the base case, a modest 25% reduction in graft loss in dnDSA-positive patients treated with increased immunosuppression resulted in 0...
November 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26967790/de-novo-dq-donor-specific-antibodies-are-associated-with-chronic-lung-allograft-dysfunction-after-lung-transplantation
#14
Jussi M Tikkanen, Lianne G Singer, S Joseph Kim, Yanhong Li, Matthew Binnie, Cecilia Chaparro, Chung-Wai Chow, Tereza Martinu, Sassan Azad, Shaf Keshavjee, Kathryn Tinckam
RATIONALE: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. OBJECTIVES: To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. METHODS: We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011...
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26951711/rabbit-antithymocyte-globulin-and-donor-specific-antibodies-in-kidney-transplantation-a-review
#15
REVIEW
Julio Pascual, Andreas Zuckermann, Arjang Djamali, Alexandre Hertig, Maarten Naesens
The mode of action of rabbit antithymocyte globulin (rATG) includes preferential inhibition of pre-existing donor-reactive memory T-cell reconstitution and possibly apoptosis of plasma cells, the source of donor specific antibodies (DSAs). In kidney transplant patients with low-strength preformed DSAs, non-comparative data have shown a low incidence of antibody-mediated rejection (ABMR) and graft survival using rATG even without desensitization procedures. For high strengths of preformed DSAs, rATG induction with more aggressive desensitization appears effective, with mixed results concerning the addition of B-cell specific agents...
April 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/26725780/acquisition-of-c3d-binding-activity-by-de-novo-donor-specific-hla-antibodies-correlates-with-graft-loss-in-nonsensitized-pediatric-kidney-recipients
#16
P Comoli, M Cioni, A Tagliamacco, G Quartuccio, A Innocente, I Fontana, A Trivelli, A Magnasco, A Nocco, C Klersy, L Rubert, M Ramondetta, M Zecca, G Garibotto, G M Ghiggeri, M Cardillo, A Nocera, F Ginevri
Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity...
July 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26680372/the-influence-of-immunosuppressive-agents-on-the-risk-of-de-novo-donor-specific-hla-antibody-production-in-solid-organ-transplant-recipients
#17
REVIEW
Jacqueline G OʼLeary, Millie Samaniego, Marta Crespo Barrio, Luciano Potena, Adriana Zeevi, Arjang Djamali, Emanuele Cozzi
Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection...
January 2016: Transplantation
https://www.readbyqxmd.com/read/26442607/onset-and-progression-of-de-novo-donor-specific-anti-human-leukocyte-antigen-antibodies-after-bk-polyomavirus-and-preemptive-immunosuppression-reduction
#18
G Dieplinger, M J Everly, K P Briley, C E Haisch, P Bolin, A Q Maldonado, W T Kendrick, S A Kendrick, C Morgan, P I Terasaki, L M Rebellato
BACKGROUND: BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies (dnDSA). PATIENTS AND METHODS: All primary renal transplants at East Carolina University from March 1999 to December 2010, with at least 1 post-transplant BKPyV viral load testing, were analyzed...
December 2015: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/26382932/early-immunosuppression-treatment-correlates-with-later-de-novo-donor-specific-antibody-development-after-kidney-and-pancreas-transplantation
#19
Ronald P Pelletier, Amer A Rajab, Alejandro Diez, Nicholas R DiPaola, Ginny L Bumgardner, Elmahdi A Elkhammas, Mitchell L Henry
BACKGROUND: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year. METHODS: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant. Recipient immunosuppressive treatment at one, three, six, and 12 months post-transplant was correlated with dnDSA incidence by univariate and multivariate analyses...
December 2015: Clinical Transplantation
https://www.readbyqxmd.com/read/26160049/relationship-among-c1q-fixing-de-novo-donor-specific-antibodies-c4d-deposition-and-renal-outcome-in-transplant-glomerulopathy
#20
REVIEW
Maria Messina, Claudia Ariaudo, Loredana Praticò Barbato, Silvia Beltramo, Gianna Mazzucco, Antonio Amoroso, Andrea Ranghino, Vincenzo Cantaluppi, Fabrizio Fop, Giuseppe Paolo Segoloni, Luigi Biancone
BACKGROUND: The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome. METHODS: We retrospectively studied 35 kidney transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined. RESULTS: Of the 35 patients with dnDSA and TG, 15 (42...
September 2015: Transplant Immunology
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