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Hla antibody monitoring

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https://www.readbyqxmd.com/read/28339671/characteristics-of-donor-specific-anti-hla-antibodies-and-outcome-in-renal-transplant-patients-treated-with-a-standardized-induction-regimen
#1
Daniel Zecher, Christian Bach, Christoph Staudner, Carsten A Böger, Tobias Bergler, Bernhard Banas, Bernd M Spriewald
Background.: Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Methods.: Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology...
February 18, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28319051/tissue-specific-exosome-biomarkers-for-noninvasively-monitoring-immunologic-rejection-of-transplanted-tissue
#2
Prashanth Vallabhajosyula, Laxminarayana Korutla, Andreas Habertheuer, Ming Yu, Susan Rostami, Chao-Xing Yuan, Sanjana Reddy, Chengyang Liu, Varun Korutla, Brigitte Koeberlein, Jennifer Trofe-Clark, Michael R Rickels, Ali Naji
In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28289413/mica-and-nkg2d-is-there-an-impact-on-kidney-transplant-outcome
#3
REVIEW
Matilde Risti, Maria da Graça Bicalho
This paper aims to present an overview of MICA and natural killer group 2 member D (NKG2D) genetic and functional interactions and their impact on kidney transplant outcome. Organ transplantation has gone from what can accurately be called a "clinical experiment" to a routine and reliable practice, which has proven to be clinically relevant, life-saving and cost-effective when compared with non-transplantation management strategies of both chronic and acute end-stage organ failures. The kidney is the most frequently transplanted organ in the world (transplant-observatory)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28274484/posttransplant-peripheral-blood-donor-specific-interferon-%C3%AE-enzyme-linked-immune-spot-assay-differentiates-risk-of-subclinical-rejection-and-de-novo-donor-specific-alloantibodies-in-kidney-transplant-recipients
#4
Elena Crespo, Paolo Cravedi, Jaume Martorell, Sergi Luque, Edoardo Melilli, Josep M Cruzado, Marta Jarque, Maria Meneghini, Anna Manonelles, Chiara Donadei, Núria Lloberas, Montse Gomà, Josep M Grinyó, Peter Heeger, Oriol Bestard
Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T-cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T-cell mediated rejection...
March 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28265581/impact-of-desensitization-on-antiviral-immunity-in-hla-sensitized-kidney-transplant-recipients
#5
Mieko Toyoda, Bong-Ha Shin, Shili Ge, James Mirocha, David Thomas, Maggie Chu, Edgar Rodriguez, Christine Chao, Anna Petrosyan, Odette A Galera, Ashley Vo, Jua Choi, Alice Peng, Joseph Kahwaji, Stanley C Jordan
Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28255002/antibody-mediated-rejection-due-to-preexisting-versus-de-novo-donor-specific-antibodies-in-kidney-allograft-recipients
#6
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)...
March 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28220766/immunological-biomarkers-and-long-term-graft-survival-prospective-follow-up-of-457-kidney-transplant-recipients
#7
Michał Ciszek, Krzysztof Mucha, Bartosz Foroncewicz, Dorota Żochowska, Maciej Kosieradzki, Tadeusz Grochowiecki, Magdalena Durlik, Andrzej Górski, Leszek Pączek
INTRODUCTION    Antibodies against donor`s human leukocyte antigens (HLA) play a significant role in the pathogenesis of antibody mediated rejection, although their role during the late post-transplant period is unknown. A non-HLA polymorphic antigenic system like major histocompatibility class I chain-related antigen A (MICA) might be another target for antibody responses involved in rejection. OBJECTIVES    We conducted a 7-year prospective study to determine the effect of positivity for anti-HLA and anti-MICA antibodies on kidney graft survival...
February 15, 2017: Polskie Archiwum Medycyny Wewnętrznej
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
#8
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/28199773/the-road-to-hla-antibody-evaluation-do-not-rely-on-mfi
#9
H Clifford Sullivan, Robert S Liwski, Robert A Bray, Howard M Gebel
Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment, but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid-phase single antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28191005/significance-of-anti-hla-antibodies-on-adult-and-pediatric-heart-allograft-outcomes
#10
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
#11
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/28151807/the-impact-of-antibodies-and-virtual-crossmatching-on-intestinal-transplant-outcomes
#12
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
#13
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/28122486/choice-of-induction-in-the-era-of-single-antigen-bead-testing-an-idiosyncratic-case-report
#14
Alexandre Hertig
Use of induction therapy after kidney transplant is based on immunologic risk status, but accurate assessment of risk in the era of advanced immunologic testing can be complex. Here, we describe the case of a young kidney recipient who had a Castleman disease, often regarded as a benign lymphoma. Our patient, a white male patient with Castleman disease, underwent a first kidney transplant with rabbit antithymocyte globulin induction but returned to dialysis after primary nonfunction occurred. A second donor became available who shared 3 class I HLA antigens with the first donor, but only low-level isolated donor-specific antibodies toward HLA-Cw were detected (mean fluorescence intensity < 1000)...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28114171/long-term-outcomes-of-kidney-transplantation-in-patients-with-high-levels-of-preformed-dsa-the-necker-high-risk-transplant-program
#15
Lucile Amrouche, Olivier Aubert, Caroline Suberbielle, Marion Rabant, Jean-Paul Duong Van Huyen, Frank Martinez, Rebecca Sberro-Soussan, Anne Scemla, Claire Tinel, Renaud Snanoudj, Julien Zuber, Ruy Cavalcanti, Marc-Olivier Timsit, Lionel Lamhaut, Dany Anglicheau, Alexandre Loupy, Christophe Legendre
BACKGROUND: There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (ABMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required. METHODS: Our high immunologic risk program included 95 patients with high peak or day-0 DSA levels (mean fluorescence intensity (MFI) > 3000) with a CDC negative crossmatch, who received a posttransplant desensitization protocol starting at day-0 with high-dose IVIg, plasma exchanges and eventually rituximab...
January 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28045875/conformational-variants-of-hla-i-antigens-on-luminex-single-antigen-beads-for-monitoring-antibodies
#16
Mepur H Ravindranath, Vadim Jucaud
No abstract text is available yet for this article.
December 31, 2016: Transplantation
https://www.readbyqxmd.com/read/27993881/flow-cytometric-panel-reactive-antibody-results-and-the-ability-to-find-transfusion-compatible-platelets-after-antibody-desensitization-for-allogeneic-bone-marrow-transplant
#17
Eric R Rosenbaum, Soumya Pandey, Terry O Harville, Gina A Drobena, Michele Cottler-Fox
BACKGROUND: Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRA(®) and Luminex(®) based Single Antigen Bead (SAB)] would also correlate with the ability to find compatible platelets for allosensitized recipients. METHODS: A female patient with myelodysplastic syndrome and a high HLA class I PRA [>90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT...
December 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27959918/the-presence-persistence-and-functional-properties-of-plasmodium-vivax-duffy-binding-protein-ii-antibodies-are-influenced-by-hla-class-ii-allelic-variants
#18
Flora S Kano, Flávia A Souza-Silva, Leticia M Torres, Barbara A S Lima, Taís N Sousa, Jéssica R S Alves, Roberto S Rocha, Cor J F Fontes, Bruno A M Sanchez, John H Adams, Cristiana F A Brito, Douglas E V Pires, David B Ascher, Ana Maria Sell, Luzia H Carvalho
BACKGROUND: The human malaria parasite Plasmodium vivax infects red blood cells through a key pathway that requires interaction between Duffy binding protein II (DBPII) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). A high proportion of P. vivax-exposed individuals fail to develop antibodies that inhibit DBPII-DARC interaction, and genetic factors that modulate this humoral immune response are poorly characterized. Here, we investigate if DBPII responsiveness could be HLA class II-linked...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27870356/clinical-and-immunological-relevance-of-antibodies-in-solid-organ-transplantation
#19
REVIEW
N K Mehra, A K Baranwal
The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection...
December 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27862352/de-novo-donor-specific-anti-hla-antibodies-after-kidney-transplantation-are-associated-with-impaired-graft-outcome-independently-of-their-c1q-binding-ability
#20
Teresa Kauke, Cornelia Oberhauser, Viviane Lin, Michaela Coenen, Michael Fischereder, Andrea Dick, Ulf Schoenermarck, Markus Guba, Joachim Andrassy, Jens Werner, Bruno Meiser, Martin Angele, Manfred Stangl, Antje Habicht
Many aspects of post-transplant monitoring of donor-specific (DSA) and non-donor-specific (nDSA) anti-HLA antibodies on renal allograft survival are still unclear. Differentiating them by their ability to bind C1q may offer a better risk assessment. We retrospectively investigated the clinical relevance of de novo C1q-binding anti-HLA antibodies on graft outcome in 611 renal transplant recipients. Acute rejection (AR), renal function, and graft survival were assessed within a mean follow-up of 6.66 years. Post-transplant 6...
November 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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