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Udeme D Ekong, Swati Antala, Laurine Bow, Doreen Sese, Raffaella Morotti, Manuel Rodriguez-Davalos, Geliang Gan, Yanhong Deng, Sukru H Emre
OBJECTIVES: To identify the risk of developing acute rejection, allograft fibrosis, and antibody-mediated rejection, a retrospective review of pediatric patients who underwent liver transplant between July 31, 1998 and February 29, 2016 and had donor-specific antibodies measured at time of liver biopsy was undertaken. MATERIALS AND METHODS: HLAMatchmaker Software ( was used to define epitope mismatches between donors and recipients and to predict de novo donor-specific antibody risk...
January 2019: Experimental and Clinical Transplantation
Yan Qin, Bo Sun, Fang Zhang, Yong Wang, Bing Shen, Yong Liu, Yifeng Guo, Yu Fan, Jianxin Qiu
BACKGROUND: Antibody-mediated rejection (AMR) can cause graft loss and reduces long-term graft survival after kidney transplantation. Human leukocyte antigen (HLA) and/or non-HLA antibodies play a key role in the pathogenesis of AMR by targeting the allograft epithelium via complement activation and complement-independent mechanisms. However, the precise mechanisms of AMR remain unclear and treatment is still limited. METHODS: In this study, we investigated the role of the endothelial-associated transcription factor Sox7 in AMR, using the anti-HLA antibody W6/32, shRNA-mediated Sox7 knockdown, and by manipulating the Notch pathway...
January 9, 2019: Experimental Cell Research
Jeffrey J Kiernan, Cynthia A Ellison, Kathryn J Tinckam
PURPOSE OF REVIEW: This review describes the utility and limitations of measure for assessing the presence, relative strength, and clinical impact of human leukocyte antigen (HLA) alloantibodies, as well as the other qualitative features of antibodies that are important considerations in assessing patient risk. RECENT FINDINGS: Using MFI as a measure of antibody amount is limited for a variety of reasons. Standardized serum manipulations such as ethylene-diamine-tetra-acetic acid treatment or serum dilution results in better definition of relationships between MFI and antibody titer or complement activation, toward greater alignment in defining positivity...
February 2019: Current Opinion in Organ Transplantation
Laura Riesco, Juan Irure, Emilio Rodrigo, Sandra Guiral, Juan Carlos Ruiz, Javier Gómez, Marcos López-Hoyos, David San Segundo
BACKGROUND: The improvement in the definition of serum anti-HLA antibodies (HLA-Abs) profiles after Luminex-assay implementation in transplant patients follow-up is clear. This success has permitted the development of hypersensitized-recipient allocation and donor-paired exchange programs improving the access to transplantation. However, non-HLA Abs have been described in transplanted patients but their effect in hypersensitized transplanted recipients is unclear. METHODS: Twenty-seven HLA hypersensitized patients awaiting for kidney transplantation (KT) were studied and 11 of them were followed after KT...
November 17, 2018: Transplant Immunology
Anthony D Vinson, Reinaldo Rampolla-Selles, E Shannon Cooper, Caroline R Alquist
Background: Acute rejection of lung allografts is an important contributor to morbidity and mortality in the transplant patient population, resulting in the dysfunction and destruction of the graft by the host's immune system via cellular or antibody-mediated mechanisms. Acute cellular rejection (ACR) is more common and better characterized than antibody-mediated rejection, which to date lacks any widely agreed upon, standardized set of diagnostic criteria. We present a case of AMR attributable to a rare phenomenon, non-human leukocyte antigen (HLA) antibodies...
2018: Ochsner Journal
Harold C Sullivan, Christina L Dean, Robert S Liwski, Shilpee Biswas, Abigail L Goodman, Scott Krummey, Howard M Gebel, Robert A Bray
Flow cytometric crossmatches (FCXM) are routinely performed to support living-donor renal transplantation. While long a laboratory mainstay, a physical crossmatch is costly, time consuming, and frequently poses interpretative conundrums with both false-positive and false- negative results. Given the increased utilization of the virtual crossmatch (vXM) in the deceased donor setting, our aim was to assess its utility in living donor evaluations. We reviewed 100 living donor FCXMs and retrospectively performed a vXM for each pair...
October 2018: Human Immunology
K Nowańska, P Donizy, K Kościelska-Kasprzak, D Kamińska, M Krajewska, O Mazanowska, K Madziarska, S Zmonarski, P Chudoba, B Małkiewicz, A Hałoń, M Klinger, M Banasik
BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies...
July 2018: Transplantation Proceedings
S Viboon, N Townamchai, S Phiancharoen, P Kupatawintu, V Dhitivat, O Nathalang
BACKGROUND: Non-HLA antibodies specific to angiotensin II type 1 receptor (AT1R-Ab) are associated with antibody-mediated rejection after kidney transplantation. This study aimed to determine the prevalence of AT1R-Ab among pre-transplantation Thai patients and to compare the association of patient demographics with AT1R-Ab levels. METHODS: This cohort study enrolled nonsensitized kidney transplant patients with negative panel reactive antibodies at King Chulalongkorn Memorial Hospital, Bangkok, Thailand...
June 2018: Transplantation Proceedings
Ji Won Min, Hyeyoung Lee, Bum Soon Choi, Cheol Whee Park, Chul Woo Yang, Yong Soo Kim, Yeong Jin Choi, Eun Jee Oh, Byung Ha Chung
BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients...
September 2018: Annals of Laboratory Medicine
Olivia N Gilbert, Patricia P Chang
a Purpose of review: This review summarizes recent data about antibodies after cardiac transplantation; what testing modalities are available and how frequently to employ them; as well as when treatment is necessary. b Recent findings: Technologies available for antibody detection have progressed over the past couple decades. New and preformed antibodies are associated with worse outcomes in transplant recipients. c Summary: The frequency of screening for post-transplant antibodies and for antibody-mediated rejection (AMR) should be based on risk stratification...
September 2017: Current Transplantation Reports
Sarah B See, Olivier Aubert, Alexandre Loupy, Yokarla Veras, Xavier Lebreton, Baoshan Gao, Christophe Legendre, Dany Anglicheau, Emmanuel Zorn
Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens. Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France...
June 2018: Journal of the American Society of Nephrology: JASN
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...
April 2018: Human Immunology
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...
March 2018: Pediatric Transplantation
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...
April 2018: Transplantation Proceedings
Kunal Yadav, Adrian Cotterell, Pamela Kimball, Laura Warmke, Melissa Contos, Gaurav Gupta, Anne King, Dhiren Kumar, Marlon Levy
This case describes a 34year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection. She later received a pancreas allograft, again with a weakly positive FCXM, without DSA. After good initial graft function, she developed hyperglycemia six weeks posttransplant. Cross-sectional imaging demonstrated non-enhancing pancreas allograft with new vein thrombosis...
April 2018: Transplant Immunology
Alison J Gareau, Chris Wiebe, Denise Pochinco, Ian W Gibson, Julie Ho, David N Rush, Peter W Nickerson
Studies investigating the potential pathogenic effects of non-HLA antibodies (Ab) have identified Ab against the angiotensin II type 1 receptor (AT1 R-Ab) as a risk factor for rejection and kidney graft loss. This study sought to validate the risk of AT1 R-Ab for acute rejection and to explore the role of other non-HLA Abs in this capacity. Pre- and post-transplant sera from a cohort of 101 patients (n=453 samples total) were tested for AT1 R-Ab and other non-HLA Ab using a commercially available ELISA kit and the Luminex platform, respectively...
February 2018: Transplant Immunology
Katherine V Gates, Naveen L Pereira, Leigh G Griffiths
Historically efforts have focused on the human leukocyte antigen (HLA) as the major cause for acute and chronic rejection following cardiac transplantation. However, rising evidence indicates that non-HLA antibodies can be both primary initiators and modifiers of antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). The purpose of this review is to assess currently available technologies for non-HLA identification and leveraging such responses toward antibody quantification. Several techniques have been used to identify antigenic determinants of recipient graft-specific non-HLA humoral immune responses, but each comes with its own set of benefits and caveats...
2017: Frontiers in Immunology
Volker Daniel, Caner Süsal, Sabine Scherer, Hien Tran, Petra Gombos, Karina Trojan, Mahmoud Sadeghi, Christian Morath, Gerhard Opelz
BACKGROUND: Non-HLA antibodies against human endothelial progenitor cells (EPC) in pre-transplant recipient serum can have a deleterious influence on the graft. EPC enriched from peripheral blood have been commonly used for EPC cross-matching. In the present study, we describe cross-matches using EPC enriched from fresh or frozen-thawed spleen cell preparations, thereby widening the sample source for deceased-donor cross-matching and retrospective studies. METHODS: EPC cross-matches were performed retrospectively using spleen cells and the flow cytometric XM-ONE cross-match test kit...
December 2017: Clinical Transplantation
Roman Reindl-Schwaighofer, Andreas Heinzel, Lorenzo Signorini, Olivier Thaunat, Rainer Oberbauer
This review focuses on the emerging concept of genomewide genetic variation as basis of an alloimmune response. Chronic antibody-mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor-specific alloantibodies is driven by indirect allorecognition of donor-derived peptides representing a form of conventional T-cell response...
March 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Jacqueline G OʼLeary, Anthony J Demetris, Aurélie Philippe, Robert Freeman, Junchao Cai, Harald Heidecke, Cory Smith, Brent Hart, Linda W Jennings, Rusan Catar, Mathew Everly, Goran B Klintmalm, Duska Dragun
BACKGROUND: Recent data have shown an increased risk for rejection, fibrosis progression, and death in liver transplantation (LT) recipients with preformed or de novo HLA donor-specific alloantibodies (DSA). However, the role of non-HLA autoantibodies and the interaction between HLA DSA and non-HLA autoantibodies remains uncharacterized. METHODS: We analyzed 1269 primary LT recipients from 1 of 2000 to 4 of 2009 with known HLA DSA status for angiotensin II type-1 receptor and endothelin-1 type A receptor autoantibodies pre-LT, and year 1 post-LT...
October 2017: Transplantation
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