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https://www.readbyqxmd.com/read/28212150/desensitization-strategies-in-the-patient-awaiting-heart-transplantation
#1
David H Chang, Jon A Kobashigawa
PURPOSE OF REVIEW: The aim of this review is to discuss the impact of antibody sensitization on heart transplant recipients. RECENT FINDINGS: We will discuss the current state of antibody identification, antibody strength and potential antibody pathogenicity. The prevalence of antibody sensitization has increased with increased utilization of mechanical circulatory support (MCS). Data on MCS-related antibody sensitization are reviewed. Important considerations to minimize the prozone effect in antibody testing will be discussed...
February 15, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28211192/racial-differences-in-incident-de-novo-donor-specific-anti-hla-antibody-among-primary-renal-allograft-recipients
#2
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/28207632/are-we-ready-for-epitope-based-hla-matching-in-clinical-organ-transplantation
#3
Rene J Duquesnoy
This overview describes recent developments demonstrating the significance of epitopes in HLA antibody responses and matching for organ transplantation. HLA epitopes are defined by molecular modeling and amino acid comparisons between HLA alleles and the HLAMatchmaker algorithm considers eplets as essential components. Each allele represents a distinct string of eplets and matching is done by aligning donor and recipient strings. Evidence is summarized how mismatched eplet loads affect antibody responses and transplant outcomes...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#4
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199784/allosensitization-following-bone-graft
#5
Eoin D O'Sullivan, Richard K Battle, Sharon Zahra, John F Keating, Lorna P Marson, David M Turner
It is recognised that patients may become sensitized to donor-specific HLA antigens as a result of previous antigenic exposures, classically through previous transplantation, pregnancy or blood transfusion. We present an unusual case of a patient who unexpectedly developed a range of anti-HLA antibodies following orthopaedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old male awaiting a renal transplantation, undergoing elective orthopaedic surgery requiring a small volume bone graft...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28198539/cytomegalovirus-infection-alters-phenotypes-of-different-%C3%AE-%C3%AE-t-cell-subsets-in-renal-transplant-recipients-with-long-term-stable-graft-function
#6
Silvia Lee, Jacquita S Affandi, Ashley B Irish, Patricia Price
Cytomegalovirus (CMV) infection alters the phenotypic profiles of T-cells and NK cells in healthy and immunocompromised individuals. Here, we examined the effects of CMV infection on the phenotype and functions of γδ T-cell subsets in renal transplant recipients (RTR) stable several years after transplantation (n = 80) and healthy controls (n = 72). Differentiation status, function, and expression of HLA-DR, CD57 and LIR-1 on Vδ2- and Vδ2+ γδ T-cells were examined in peripheral blood cells using flow cytometry...
February 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28191005/significance-of-anti-hla-antibodies-on-adult-and-pediatric-heart-allograft-outcomes
#7
REVIEW
Massimo Mangiola, Marilyn Marrari, Brian Feingold, Adriana Zeevi
As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient's neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection...
2017: Frontiers in Immunology
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
#8
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
#9
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/28166393/donor-specific-antibodies-c1q-binding-improvement-in-kidney-graft-management
#10
Sylvie Ferrari-Lacraz
The diagnosis of acute antibody mediated rejection (ABMR) after kidney transplantation is based on three parameters: 1) decreased renal function, 2) histopathological signs of rejection, 3) presence of Donor Specific Antibody (DSA) [1]. Patient survival, as well as graft survival have improved since 5 to 10 years [2], thanks to several factors, including better management of patients, better immunosuppressive regimens, detection and avoidance of DSA. Although anti-HLA antibodies follow-up have improved ABMR management, its treatment remains challenging, and outcome may be worsened because of a delay in the diagnosis...
February 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28165448/effective-desensitization-of-donor-specific-hla-antibodies-using-platelet-transfusion-bearing-targeted-hla-in-a-case-of-hla-mismatched-allogeneic-stem-cell-transplantation
#11
T Yamashita, K Ikegame, H Kojima, H Tanaka, K Kaida, T Inoue, H Ogawa
No abstract text is available yet for this article.
February 6, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28164503/association-of-hla-types-with-non-specific-binding-of-negative-control-beads-in-luminex-panel-reactive-antibody-pra-screening-assay
#12
Nuri Lee, Hee Sue Park, Ji Won In, Eun Youn Roh, Sue Shin, Kyoung Un Park, Eun Young Song
BACKGROUND: Luminex panel reactive antibody (PRA) screening assays using microbeads are widely used for organ transplantation. Anti-HLA serum reactivity is calculated by correcting for non-specific binding to the negative control (NC) beads. High mean fluorescence intensity (MFI) value of NC beads are observed in some patients and can result in false negative results in the PRA screening assay. We analyzed the clinical characteristics and HLA types of those patients with high MFI values of NC beads...
January 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#13
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28158255/improvement-in-the-definition-of-anti-hla-antibody-profile-in-highly-sensitized-patients
#14
Juan Irure, Esther Asensio, Emilio Rodrigo, Íñigo Romón, Javier Gómez, Manuel Arias, Marcos López-Hoyos, David San Segundo
The definition of anti-HLA antibody profile in highly sensitized patients on a waiting list is crucial when virtual crossmatch is used in organ allocation systems, but also when used to identify the true deleterious anti-HLA antibodies. Here we propose different levels of risk based on the results of anti-HLA antibody testing in neat serum (N) and after sera dilution (DIL) and C1q test in 18 highly sensitized patients. This group was heterogeneous in terms of anti-HLA antibody titers and their ability to fix complement...
2017: PloS One
https://www.readbyqxmd.com/read/28151807/the-impact-of-antibodies-and-virtual-crossmatching-on-intestinal-transplant-outcomes
#15
Elaine Y Cheng, Bernard J DuBray, Douglas G Farmer
PURPOSE OF REVIEW: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies. RECENT FINDINGS: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes...
February 1, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28148598/gene-expression-profiling-for-the-identification-and-classification-of-antibody-mediated-heart-rejection
#16
Alexandre Loupy, Jean Paul Duong Van Huyen, Luis Hidalgo, Jeff Reeve, Maud Racapé, Olivier Aubert, Jeffery M Venner, Konrad Falmuski, Marie-Cécile Bories, Thibaut Beauscart, Romain Guillemain, Arnaud François, Sabine Pattier, Claire Toquet, Arnaud Gay, Philippe Rouvier, Shaida Varnous, Pascal Leprince, Jean-Philippe Empana, Carmen Lefaucheur, Patrick Bruneval, Xavier Jouven, Philip F Halloran
BACKGROUND: -Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains regarding the pathophysiology of AMR and how detection of immune activity, injury degree and stage could be improved by intragraft gene expression profiling. METHODS: -We prospectively monitored 617 heart transplant recipients referred from four French transplant centers (January 1st 2006 - January 1st 2011) for AMR. We compared patients with AMR (n=55) to a matched control group of 55 patients without AMR...
February 1, 2017: Circulation
https://www.readbyqxmd.com/read/28144069/a-severe-mycoplasma-pneumoniae-pneumonia-inducing-an-acute-antibody-mediated-pulmonary-graft-rejection
#17
Sarah Démir, Julien Saison, Agathe Sénéchal, Jean-Francois Mornex
A 40-year-old cystic fibrosis woman with a history of double-lung transplantation 2 years previously was admitted for a progressive respiratory distress. Physical examination revealed fever (39°C) and diffuse bilateral lung crackles. Laboratory findings included severe hypoxemia and inflammatory syndrome. Bronchoalveolar lavage and serological test were positive for mycoplasma pneumonia. As the patient did not improve after 3 days of antibiotics and donor-specific HLA antibodies had been detected, an acute antibody-mediated graft rejection was treated with high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab...
January 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28135784/morphologic-patterns-and-treatment-of-transplant-glomerulopathy-a-retrospective-analyse
#18
Rui Abreu, Fernanda Carvalho, Helena Viana, Isabel Mesquita, Marília Possante, Inês Aires, Fernando Caeiro, Cecília Silva, Patrícia Cotovio, Aníbal Ferreira, Francisco Remédio, Fernando Nolasco
Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7,1 (3,6 - 11,8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10,4%; cg2=20,8%; cg3=68,8%)...
January 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28133619/from-humoral-theory-to-performant-risk-stratification-in-kidney-transplantation
#19
REVIEW
C Lefaucheur, D Viglietti, M Mangiola, A Loupy, A Zeevi
The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28129605/mesenchymal-stem-cells-upregulate-treg-cells-via-shla-g-in-sle-patients
#20
Chen Chen, Jun Liang, Genhong Yao, Haifeng Chen, Bingyu Shi, Zhuoya Zhang, Cheng Zhao, Huayong Zhang, Lingyun Sun
BACKGROUND: Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. OBJECTIVES: To explore whether sHLA-G is involved in upregulating effects of MSCs on Treg, which contributes to therapeutic effects of MSCs transplantation in SLE...
January 24, 2017: International Immunopharmacology
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