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Transplant antibody desensitization

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https://www.readbyqxmd.com/read/28348361/the-impact-of-donor-specific-anti-human-leukocyte-antigen-hla-antibody-rebound-on-the-risk-of-antibody-mediated-rejection-in-sensitized-kidney-transplant-recipients
#1
Kyo Won Lee, Jae Berm Park, Chan Woo Cho, Nuri Lee, Heejin Yoo, Kyunga Kim, Hyojun Park, Eun Suk Kang, Wooseong Huh, Sungjoo Kim
BACKGROUND Donor-specific anti-HLA antibody (DSA) detected on Luminex-based single antigen assay (LSA) has become the subject of desensitization based upon the results of previous studies. We retrospectively investigated the impact of preoperative DSA on the incidence of antibody mediated rejection (AMR) in patients desensitized using a protocol based on rituximab and rabbit antithymocyte globulin (rATG). MATERIAL AND METHODS Nine patients (Group 1, 9/327, 2.8%) were complement dependent cytotoxicity crossmatch (CDC-XM) positive and underwent desensitization with rituximab (375 mg/m²), intravenous immunoglobulin (IVIG; 400 mg/kg), plasmapheresis, and rATG...
March 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28340817/efficacy-and-safety-of-atg-fresenius-as-an-induction-agent-in-living-donor-kidney-transplantation
#2
M Yilmaz, T Ö Sezer, E Günay, I Solak, A Çeltik, C Hoşcoşkun, H Töz
BACKGROUND: Induction therapy is mostly recommended for deceased-donor transplantation, whereas it has some controversies in live-donor transplantation. In this study, we described the outcomes of live-donor renal transplant recipients who received ATG-Fresenius (ATG-F) induction. METHODS: Live-donor transplantations in patients over 18 years old with ATG-F induction between 2009 and 2015 were included. All patients received quadruple immunosuppression, one of which was ATG-F induction...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28339910/rituximab-and-hepatitis-b-reactivation-in-hbsag-negative-anti-hbc-positive-kidney-transplant-recipients
#3
Juhan Lee, Jun Yong Park, Kyu Ha Huh, Beom Seok Kim, Myoung Soo Kim, Soon Il Kim, Sang Hoon Ahn, Yu Seun Kim
Background.: Hepatitis B virus (HBV) reactivation is a well-known complication of immunosuppressive therapy. Although rituximab is increasingly used for desensitization of ABO-incompatible or positive crossmatch kidney transplantation, the risk of HBV reactivation in hepatitis B surface antigen (HBsAg)-negative/hepatitis B core antibody (anti-HBc)-positive kidney transplant patients receiving rituximab desensitization remains undetermined. Methods.: We analysed 172 resolved HBV patients who underwent living donor kidney transplantation between 2008 and 2014...
April 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#4
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28321223/abo-incompatible-kidney-transplantation
#5
REVIEW
Christian Morath, Martin Zeier, Bernd Döhler, Gerhard Opelz, Caner Süsal
ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28306593/current-concepts-for-sensitized-patients-before-transplantation
#6
Dael Geft, Jon Kobashigawa
PURPOSE OF REVIEW: Antibody allosensitization poses a major immunologic challenge for patients awaiting heart transplantation. It is associated with significant morbidity and mortality for both pretransplant and posttransplant patients by prolonging wait times to transplant and increasing posttransplant rejection and vasculopathy. Many questions remain regarding methods and interpretation of antibody detection, the relevance of sensitization in specific patient populations such as those with mechanical circulatory support and the ideal strategies for desensitization...
March 16, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28284304/kidney-paired-exchange-and-desensitization-strategies-to-transplant-the-difficult-to-match-kidney-patients-with-living-donors
#7
REVIEW
Thomas A Pham, Jacqueline I Lee, Marc L Melcher
With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible...
January 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28265581/impact-of-desensitization-on-antiviral-immunity-in-hla-sensitized-kidney-transplant-recipients
#8
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/28260472/anti-hla-antibody-levels-are-associated-with-the-risk-of-graft-failure-after-allogeneic-hematopoietic-stem-cell-transplant
#9
Bilkay Basturk, Mutlu Kasar, Mahmut Yeral, Miray Kavuzlu
OBJECTIVES: Allogeneic hematopoietic stem cell transplant provides a curative treatment for a considerable amount of hematologic diseases, and it is widely used today. Successful allogeneic stem cell transplant can be compromised by treatment-related toxicity, graft-versus-host disease, infectious complications, disease relapse, and graft failure. Primary graft failure is an important cause of hematopoietic stem cell transplant failure. Primary graft failure correlates with the level of complement-binding, donor-specific anti-HLA antibodies prior to transplant...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28213687/ofatumumab-for-the-treatment-of-childhood-nephrotic-syndrome
#10
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...
May 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28212150/desensitization-strategies-in-the-patient-awaiting-heart-transplantation
#11
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
#12
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
#13
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
#14
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...
May 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28127571/desensitization-overcoming-the-immunologic-barriers-to-transplantation
#15
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
#16
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
#17
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...
February 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#18
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
#19
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)...
March 2017: Human Immunology
https://www.readbyqxmd.com/read/28003816/hla-mismatching-strategies-for-solid-organ-transplantation-a-balancing-act
#20
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
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