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Transplant antibody desensitization

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https://www.readbyqxmd.com/read/28213687/ofatumumab-for-the-treatment-of-childhood-nephrotic-syndrome
#1
Chia-Shi Wang, Rochelle Schmidt Liverman, Rouba Garro, Roshan Punnoose George, Anastacia Glumova, Alana Karp, Stephanie Jernigan, Barry Warshaw
BACKGROUND: Ofatumumab is a humanized anti-CD20 monoclonal antibody that has recently garnered interest as a potential therapeutic agent for nephrotic syndrome. We report our center's experience in administering ofatumumab to five pediatric patients with idiopathic nephrotic syndrome. METHODS: Between March 2015 and November 2016, five patients were treated with ofatumumab. One patient had post-transplant recurrent focal segmental glomerulosclerosis (FSGS) which had been resistant to plasmapheresis and numerous immunosuppressive agents...
February 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28212150/desensitization-strategies-in-the-patient-awaiting-heart-transplantation
#2
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/28191005/significance-of-anti-hla-antibodies-on-adult-and-pediatric-heart-allograft-outcomes
#3
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/28165448/effective-desensitization-of-donor-specific-hla-antibodies-using-platelet-transfusion-bearing-targeted-hla-in-a-case-of-hla-mismatched-allogeneic-stem-cell-transplantation
#4
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/28162932/multicenter-evaluation-of-a-national-organ-sharing-policy-for-highly-sensitized-patients-listed-for-heart-transplantation-in-canada
#5
Brian Clarke, Anique Ducharme, Nadia Giannetti, Daniel Kim, Michael McDonald, Peter Pflugfelder, Miroslaw Rajda, Mario Sénéchal, Ellie Stadnick, Mustafa Toma, Shelley Zieroth, Debra Isaac
BACKGROUND: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access. In this study, we describe patient characteristics and outcomes of those transplanted as Status 4S in Canada...
January 6, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28127571/desensitization-overcoming-the-immunologic-barriers-to-transplantation
#6
REVIEW
Supreet Sethi, Jua Choi, Mieko Toyoda, Ashley Vo, Alice Peng, Stanley C Jordan
HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells...
2017: Journal of Immunology Research
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
#7
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/28110970/-plasma-exchange-in-nephrology-indications-and-technique
#8
Christophe Ridel, Sébastien Kissling, Laurent Mesnard, Alexandre Hertig, Éric Rondeau
Plasma exchange is a non-selective apheresis technique that can be performed by filtration or centrifugation allowing rapid purification of high molecular weight pathogens. An immunosuppressive treatment is generally associated to reduce the rebound effect of the purified substance. Substitution solutes such as human albumin and macromolecules are needed to compensate for plasma extraction. Compensation by viro-attenuated plasma is reserved solely for the treatment of thrombotic microangiopathies or when there is a risk of bleeding, because this product is very allergenic and expensive...
January 16, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#9
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
#10
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
#11
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
#12
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
#13
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-7-year-single-center-experience
#14
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 heart transplant 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 was associated with IFI (P=...
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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