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Transplant antibody desensitization

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https://www.readbyqxmd.com/read/29731097/desensitization-with-the-use-of-an-antibody-removal-free-protocol-in-abo-incompatible-kidney-transplant-recipients-with-a-low-anti-a-b-antibody-titer
#1
K Nanmoku, T Shinzato, T Kubo, T Shimizu, T Kimura, T Yagisawa
BACKGROUND: Desensitization for ABO-incompatible (ABOi) kidney transplantation mainly comprises removal of antibodies with the use of apheresis and suppression of antibody (Ab) production with the use of rituximab. This study aimed to estimate the outcomes of ABOi kidney transplantation with the use of an Ab removal-free protocol to avoid complications associated with apheresis. METHODS: A total of 32 de novo consecutive adults who underwent ABOi living-donor kidney transplantation were retrospectively evaluated...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29676812/impact-of-pretransplant-donor-specific-antibodies-on-kidney-allograft-recipients-with-negative-flow-cytometry-crossmatches
#2
Hyunwook Kwon, Young Hoon Kim, Ji Yoon Choi, Sung Shin, Joo Hee Jung, Su-Kil Park, Duck Jong Han
The Luminex test can detect low levels of donor-specific antibody (DSA) that cannot be detected by flow-cytometric crossmatching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA-negative and 81 (14.1%) were DSA-positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the two groups (P = 0...
April 20, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29676803/outcome-of-the-risk-stratified-desensitization-protocol-in-donor-specific-antibody-positive-living-kidney-transplant-recipients-a-retrospective-study
#3
Daigo Okada, Masayoshi Okumi, Yoichi Kakuta, Kohei Unagami, Junpei Iizuka, Toshio Takagi, Hideki Ishida, Kazunari Tanabe
Acceptable outcomes of donor-specific antibody (DSA)-positive living kidney transplantation (LKT) have recently been reported. However, LKT in crossmatch (XM)-positive patients remains at high-risk and requires an optimal desensitization protocol. We report our intermediate-term outcomes of XM-positive LKT versus XM-negative LKT in patients who underwent LKT between January 2012 and June 2015 in our institution. The rate of acute antibody-mediated rejection (ABMR) within 90 days post-operation, graft function, and patient and graft survival rates at 4 years were investigated...
April 20, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29620615/long-term-outcomes-of-abo-incompatible-pediatric-living-donor-liver-transplantation
#4
Masaki Honda, Yasuhiko Sugawara, Masashi Kadohisa, Keita Shimata, Masataka Sakisaka, Daiki Yoshii, Keiichi Uto, Shintaro Hayashida, Yuki Ohya, Hidekazu Yamamoto, Hirotoshi Yamamoto, Yukihiro Inomata, Taizo Hibi
BACKGROUND: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) have been performed to compensate for donor shortage. To date, few studies have reported detailed B cell desensitization protocols and long-term outcomes of ABOi pediatric LDLT. METHODS: Twenty-nine pediatric ABOi LDLT recipients were retrospectively analyzed. We compared the clinical outcomes between ABOi (n = 29) and non-ABOi (n = 131) pediatric LDLT recipients. Furthermore, we evaluated the safety and efficacy of our rituximab-based regimen for ABOi pediatric LDLT (2 ≤ age < 18, n = 10)...
April 3, 2018: Transplantation
https://www.readbyqxmd.com/read/29579822/highly-hla-sensitized-kidney-transplant-patients-in-a-transplant-center
#5
P K Garcia, J Toro, C Borda, C Gonzalez, M P Rodriguez, K Contreras
INTRODUCTION: Approximately 10% to 30% of patients on renal transplant waiting lists are sensitized, which gives them more time on the waiting list. Transplantation in this setting has a greater risk of rejection and decreased graft survival. New strategies of donor allocation through virtual crossmatching and optimization of immunosuppressive therapies in induction and maintenance have allowed the allocation of organs for this population, which in other circumstances would not be chosen for a kidney transplant...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29529999/prevalence-of-pre-transplant-anti-hla-antibodies-and-their-impact-on-outcomes-in-lung-transplant-recipients
#6
Ji Eun Park, Chi Young Kim, Moo Suk Park, Joo Han Song, Young Sam Kim, Jin Gu Lee, Hyo Chae Paik, Song Yee Kim
BACKGROUND: Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. METHODS: A single-center retrospective study was conducted...
March 12, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29519740/peri-operative-desensitization-a-promising-strategy-for-overcoming-the-antibody-barrier-in-heart-transplantation
#7
EDITORIAL
Jignesh K Patel
No abstract text is available yet for this article.
May 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29407331/safety-and-efficacy-of-induction-therapy-with-thymoglobulin-in-ab0-incompatible-kidney-transplantation
#8
A L Herzog, C Kalogirou, C Wanner, K Lopau
INTRODUCTION: Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell-depleting anti-CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29405445/the-possible-critical-role-of-t-cell-help-in-dsa-mediated-graft-loss
#9
REVIEW
Caner Süsal, Antonij Slavcev, Lien Pham, Martin Zeier, Christian Morath
In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect...
February 6, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29399625/successful-desensitization-of-t-cell-flow-cytometry-crossmatch-positive-renal-transplant-recipients-using-plasmapheresis-and-super-high-dose-intravenous-immunoglobulin
#10
Yoichi Kakuta, Shigeru Satoh, Yoshihiko Watarai, Atsushi Aikawa, Kazunari Tanabe, Hiroshi Harada, Takashi Yagisawa, Hideki Ishida, Masayoshi Okumi, Shiro Takahara
Background: High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation. Methods: Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1...
January 2018: Transplantation Direct
https://www.readbyqxmd.com/read/29380556/pediatric-abo-incompatible-kidney-transplantation-evolving-with-the-advancing-apheresis-technology-a-single-center-experience
#11
Sidharth Kumar Sethi, Shyam Bihari Bansal, Nikita Wadhwani, Aseem Tiwari, Dinesh Arora, Reetesh Sharma, Ashish Nandwani, Dinesh Kumar Yadav, Amit Kumar Mahapatra, Manish Jain, Pranaw Jha, Prasun Ghosh, Anil Bhan, Maninder Dhaliwal, Veena Raghunathan, Vijay Kher
Recent literature has endorsed favorable outcomes following ABOi kidney transplantation in pediatric population. Nevertheless, reluctance to pursue an ABOi still remains pervasive. This could be ascribed to various legitimate reasons, namely less extensive pediatric ABOi data, technical difficulties encountered during PP, cost restraints, and concerns regarding higher rates of antibody-mediated rejection, infectious complications, and post-transplant lymphoproliferative disorder as compared to adults. However, given the similar excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians should consider this option sooner if a compatible donor or swap is not available...
May 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29298238/desensitization-and-prevention-of-antibody-mediated-rejection-in-vascularized-composite-allotransplantation-by-syngeneic-hematopoietic-stem-cell-transplantation
#12
Howard D Wang, Samuel A J Fidder, Devin T Miller, Georg J Furtmüller, Ali R Ahmadi, Felix Nägele, Joseph Lopez, Amy Quan, Joshua Budihardjo, Denver M Lough, Burcu Akpinarli, Joanna W Etra, Dalibor Vasilic, Giorgio Raimondi, W P Andrew Lee, Robert A Montgomery, Zhaoli Sun, Gerald Brandacher
BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection. Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent antibody-mediated rejection in VCA. METHODS: Skin transplants from Dark Agouti to Lewis rats were performed for sensitization...
April 2018: Transplantation
https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#13
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29277957/early-post-transplant-diagnosis-of-cytomegalovirus-esophagitis-in-an-abo-incompatible-kidney-transplant-recipients-a-case-report
#14
Masahiko Yazawa, Hideo Sasaki, Yuko Sakurai, Hiroya Kudo, Ryuto Nakazawa, Tatsuya Chikaraishi, Yugo Shibagaki
Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation...
December 26, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29222316/hla-donor-specific-antibodies-in-allogeneic-hematopoietic-stem-cell-transplantation-challenges-and-opportunities
#15
REVIEW
Douglas E Gladstone, Maria P Bettinotti
Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. More recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29207227/first-case-report-of-using-ofatumumab-in-kidney-transplantation-ab0-incompatible
#16
Nicoletta Mancianti, Giulio Monaci, Fabio Rollo, Paola Buracchi, Andrea Guarnieri, Marina Di Luca, Mauro Martello, Guido Garosi
Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment...
December 5, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29176362/significance-of-biologics-in-renal-transplantation-past-present-and-future
#17
Ivica Grgic, Anil Chandraker
PURPOSE OF REVIEW: Finding the right immunosuppressive approach for the individual transplant patient is of utmost importance. In truth, a 'one size fits all' does not exist, and as patients differ, so should therapeutic suppression of the immune system be individualized. For over three decades, biologics have been a central component of transplant immunosuppression. Our growing knowledge of immunological processes combined with biotechnological advances is leading to promising new therapeutic concepts and possibilities including novel biologics...
February 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29165070/bortezomib-in-kidney-transplant-current-use-and-perspectives
#18
Lucio R Requiao-Moura, Taina V de Sandes-Freitas, Gessika Marcelo-Gomes, Erika B Rangel
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting...
2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29140548/a-phase-ib-open-label-single-arm-study-to-assess-the-safety-pharmacokinetics-and-impact-on-humoral-sensitization-of-sanguinate-infusion-in-patients-with-end-stage-renal-disease
#19
Bassam G Abu Jawdeh, Ervin Steve Woodle, Abbie D Leino, Paul Brailey, Simon Tremblay, Tonya Dorst, Mouhamad H Abdallah, Amit Govil, Daniel Byczkowski, Hemant Misra, Abraham Abuchowski, Rita R Alloway
The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg)...
January 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29053910/a-simplified-protocol-using-rituximab-and-immunoglobulin-for-abo-incompatible-low-titre-living-donor-liver-transplantation
#20
Seong Hoon Kim, Eung Chang Lee, Jae Ryong Shim, Sang Jae Park
BACKGROUND & AIMS: No consensus has been reached regarding optimal treatment strategies for ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). We introduce a simplified protocol using rituximab and intravenous immunoglobulin (IVIG). METHODS: Data were analysed on adult patients who underwent ABO-I LDLT of which protocol added rituximab (300 mg/m(2) ) before surgery and IVIG (0.8 g/kg) on post-operative days 1 and 4 to the conventional immunosuppressive regimen used in ABO-compatible (ABO-C) LDLT, without plasmapheresis, splenectomy or graft local infusion...
October 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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