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Transplant antibody desensitization

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https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#1
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28069404/calculated-panel-reactive-antibody-with-decimals-a-refined-metric-of-access-to-transplantation-for-highly-sensitized-candidates
#2
Evan P Kransdorf, Marcelo J Pando
The use of the calculated panel reactive antibody (CPRA) value and the implementation of allocation points for sensitized candidates by the United Network for Organ Sharing (UNOS) have improved access to kidney transplantation for highly sensitized candidates (98% CPRA and above). Despite this, a large population of highly sensitized candidates remain awaiting transplantation. To better define this population, we propose the use of two refinements of the standard UNOS CPRA, the CPRA with decimals or CPRAd, and the likelihood of a compatible donor (LCD)...
January 6, 2017: Human Immunology
https://www.readbyqxmd.com/read/28003816/hla-mismatching-strategies-for-solid-organ-transplantation-a-balancing-act
#3
REVIEW
Andrea A Zachary, Mary S Leffell
HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27995324/hla-epitope-matching-in-pediatric-renal-transplantation
#4
Matthew P Sypek, Peter Hughes, Joshua Y Kausman
Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications...
December 19, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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
#5
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/27943503/invasive-fungal-infection-after-heart-transplantation-a-seven-year-single-center-experience
#6
Ignacio A Echenique, Michael P Angarone, Robert A Gordon, Jonathan Rich, Allen S Anderson, Edwin C McGee, Travis O Abicht, Joseph Kang, Valentina Stosor
BACKGROUND: Invasive fungal infections (IFIs) are an infrequent but major complication of heart-transplantation (HT). We sought to describe the epidemiology at our institution. METHODS: A prospective cohort study of 159 HT recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: By univariate analysis, Hispanic ethnicity/race was associated with IFI (P=0...
December 10, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/27932097/desensitization-protocol-in-recipients-of-deceased-kidney-donor-with-donor-specific-antibody-low-titers
#7
J Kanter Berga, A Sancho Calabuig, E Gavela Martinez, N Puig Alcaraz, A Avila Bernabeu, J Crespo Albiach, P Molina Vila, S Beltrán Catalan, L Pallardó Mateu
BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27890719/casting-a-smaller-net-into-a-bigger-donor-pool-a-single-center-s-experience-with-the-new-kidney-allocation-system
#8
Julie A Houp, Karl P Schillinger, Andrew J Eckstein, Renato M Vega, Niraj M Desai, Bonnie E Lonze, Annette M Jackson
The new kidney allocation system (KAS) provides additional allocation points for candidates with broad HLA sensitization in an effort to increase transplant rates for this underserved population. Following the implementation of KAS, our center lowered the HLA antibody threshold for listing unacceptable antigens from a cytotoxicity crossmatch level to a flow cytometric crossmatch level increasing Calculated Panel Reactive Antibody (CPRA) values and allocation points, yet restricting acceptable donor HLA phenotypes...
November 24, 2016: Human Immunology
https://www.readbyqxmd.com/read/27872835/six-end-stage-renal-disease-patients-benefited-from-first-non-simultaneous-single-center-6-way-kidney-exchange-transplantation-in-india
#9
Vivek B Kute, Himanshu V Patel, Umesh T Varyani, Pankaj R Shah, Pranjal R Modi, Veena R Shah, Sayyed J Rizvi, Bipin C Pal, Priya S Shah, Pavan S Wakhare, Vijay A Ghodela, Saiprasad G Shinde, Varsha B Trivedi, Minaxi H Patel, Hargovind L Trivedi
AIM: To avoid desensitization protocols and ABO incompatible kidney transplantation (KT) due to high costs and increased risk of infections from intense immunosuppression. METHODS: We present institutional ethical review board - approved study of single center 6-way kidney exchange transplantation. The participants comprised ABO incompatibility (n = 1); positive cross-match and/or presence of donor specific antibody (n = 5). The average time required from registration in kidney paired donation (KPD) registry to find suitable donors was 45 d and time required to perform transplants after legal permission was 2 mo...
November 6, 2016: World Journal of Nephrology
https://www.readbyqxmd.com/read/27803919/increasing-access-to-kidney-transplantation-for-sensitized-recipient-through-three-way-kidney-paired-donation-with-desensitization-the-first-indian-report
#10
Vivek B Kute, Himanshu V Patel, Pankaj R Shah, Pranjal R Modi, Veena R Shah, Sayyed J Rizvi, Bipin C Pal, Manisha P Modi, Priya S Shah, Umesh T Varyani, Pavan S Wakhare, Saiprasad G Shinde, Viajay A Ghodela, Minaxi H Patel, Varsha B Trivedi, Hargovind L Trivedi
The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient...
October 16, 2016: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/27788819/safety-and-efficacy-of-immunoadsorption-in-heart-transplantation-program
#11
T Gazdic, I Malek, L Pagacova, A Slavcev, L Voska, M Hegarova, L Hoskova, M Kubanek, J Pirk
BACKGROUND: Antibody-mediated rejection (AMR) is a serious complication of organ transplantation, and its treatment is complex. The aim of this study was to assess immunoadsorption (IA) for treatment-immunized patients before heart transplantation (HTX) and as the first step of AMR treatment after HTX. METHODS: The cohort consisted of 10 patients (8 men, 2 women; age range, 20-57 years). For 3 of these patients, IA was included in the desensitization protocol before HTX; for 7 patients, IA was the first step of the treatment protocol...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27742824/renal-transplantation-in-sensitized-children-and-young-adults-a-nationwide-approach
#12
Luca Dello Strologo, Luisa Murer, Isabella Guzzo, Federica Morolli, Annalisa M V Pipicelli, Elisa Benetti, Germana Longo, Sara Testa, Andrea Ricci, Fabrizio Ginevri, Luciana Ghio, Massimo Cardillo, Antonina Piazza, Alessandro Nanni Costa
BACKGROUND: High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes. Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. METHODS: In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%...
October 14, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27670824/-immunology-and-immunosuppression-in-kidney-transplantation-abo-and-hla-incompatible-kidney-transplantation
#13
F Kleinclauss, A Frontczak, N Terrier, R Thuret, M-O Timsit
OBJECTIVES: To perform a state of the art about immunological features in renal transplantation, immunosuppressive drugs and their mechanisms of action and immunologically high risk transplantations such as ABO and HLA-incompatible transplantation. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "allogenic response; allograft; immunosuppression; ABO incompatible transplantation; donor specific antibodies; HLA incompatible; desensitization; kidney transplantation"...
November 2016: Progrès en Urologie
https://www.readbyqxmd.com/read/27636930/-renal-transplantation-in-recipients-with-moderate-presensitization
#14
A V Vatazin, A B Zul'karnaev
AIM: to comparatively assess desensitization schemes with and without plasmapheresis in patients with low presensitization. SUBJECTS AND METHODS: The investigators studied the efficiency of the two desensitization schemes (cascade plasma filtration + intravenous immunoglobulin used in a dose of 100 mg/kg in 19 patients (a study group; panel reactive antibodies (PRA) 25.1±6.1%) versus 2 g/kg in 23 patients (a comparison group, PRA 18.9±4.4%). The crossmatch reaction was negative in both groups...
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/27585679/desensitization-protocol-enabling-pediatric-crossmatch-positive-renal-transplantation-successful-hla-antibody-incompatible-renal-transplantation-of-two-highly-sensitized-children
#15
Anna M Adamusiak, Jelena Stojanovic, Olivia Shaw, Robert Vaughan, Neil J Sebire, Martin Drage, Nicos Kessaris, Stephen D Marks, Nizam Mamode
BACKGROUND: Renal transplantation improves quality of life (QoL) and survival in children requiring renal replacement therapy (RRT). Sensitization with development of a broad-spectrum of anti-HLA antibodies as a result of previous transplantation or after receiving blood products is an increasing problem. There are no published reports of desensitization protocols in children allowing renal transplantation from HLA-antibody-incompatible living donors. METHODS: We adopted our well-established adult desensitization protocol for this purpose and undertook HLA antibody-incompatible living donor renal transplants in two children: a 14-year-old girl and a 13-year-old boy...
February 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27542515/repeated-cycles-of-high-dose-intravenous-immunoglobulin-and-plasmapheresis-for-treatment-of-late-antibody-mediated-rejection-of-renal-transplants
#16
Chih-Yuan Lee, Wei-Chou Lin, Ming-Shiou Wu, Ching-Yao Yang, Chi-Chuan Yeh, Meng-Kun Tsai
BACKGROUND/PURPOSE: Intravenous immunoglobulin (IVIG) plays a central role in the treatment of antibody-mediated rejection (AMR) of renal allografts, but the treatment outcomes for late AMR (>6 months after transplantation) are poor. METHODS: We performed a retrospective study to assess the response patterns of IVIG-based (2 g/kg) desensitization for late AMR. Patients who received desensitization after the pathological diagnosis of late AMR positive for complement component C4d were grouped as the Desensitized Group and compared to a historical Control Group with complement component C4d positivity in retrospective stainings...
October 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/27534951/results-of-a-multicenter-prospective-clinical-study-in-japan-for-evaluating-efficacy-and-safety-of-desensitization-protocol-based-on-rituximab-in-abo-incompatible-kidney-transplantation
#17
Kota Takahashi, Kazuhide Saito, Shiro Takahara, Shohei Fuchinoue, Takashi Yagisawa, Atsushi Aikawa, Yoshihiko Watarai, Norio Yoshimura, Kazunari Tanabe, Kunio Morozumi, Motohide Shimazu
BACKGROUND: Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy...
August 17, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27529314/six-year-outcomes-in-broadly-hla-sensitized-living-donor-transplant-recipients-desensitized-with-intravenous-immunoglobulin-and-rituximab
#18
Joseph Kahwaji, Stanley C Jordan, Reiad Najjar, Patarapha Wongsaroj, Jua Choi, Alice Peng, Rafael Villicana, Ashley Vo
Desensitization with intravenous immunoglobulin (IVIG) and rituximab can improve transplantation rates in broadly sensitized kidney transplant recipients. However, long-term outcomes are lacking. Here we analyze long-term outcomes in living donor kidney transplant recipients desensitized with this regimen and compare them to low-risk recipients. Living donor kidney transplants that took place between July 2006 and December 2010 were considered retrospectively. The primary end point of the study was death-censored allograft survival at last follow-up...
December 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27517505/donor-specific-antibodies-and-antibody-mediated-rejection-in-vascularized-composite-allotransplantation
#19
Annemarie Weissenbacher, Alexandre Loupy, Anil Chandraker, Stefan Schneeberger
PURPOSE OF REVIEW: The presence of donor-specific antibodies (DSA) increases the risk of graft failure. Although DSA characteristics, human leukocyte antigen class specificity, mean fluorescence intensity and immunoglobulin G subclasses, and their impact on the graft are quite well studied in solid organ transplants, very little information is known about their impact on vascularized composite allotransplantation (VCA). The aim of this review is to highlight recent publications regarding occurrence and effects of DSA, their follow-up and treatment in the field of VCA...
October 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27512872/successful-kidney-transplantation-after-desensitization-in-a-patient-with-positive-flow-crossmatching-and-donor-specific-anti-hla-dp-antibody-a-case-report
#20
Seung Hwan Song, Borae G Park, Juhan Lee, Myoung Soo Kim, Yu Seun Kim, Hyon-Suk Kim
BACKGROUND: Traditionally, the presence of antibodies against human leukocyte antigen (HLA)-C and DP was considered to be associated with only a low risk of antibody-mediated rejection (ABMR) in kidney transplantation (KT), because the antigenicities of these proteins are weak. However, the clinical effects of HLA-C and -DP donor-specific HLA antibodies (DSHAs) have recently been reevaluated. METHODS: Here, we report the case of a retransplant patient with positive flow cytometry crossmatch (FCXM) and high level of HLA-DP DSHA who was desensitized using rituximab, plasmapheresis, and intravenous immunoglobulin...
August 2016: Medicine (Baltimore)
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