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Transplant antibody desensitization

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https://www.readbyqxmd.com/read/29298238/desensitization-and-prevention-of-antibody-mediated-rejection-in-vascularized-composite-allotransplantation-by-syngeneic-hematopoietic-stem-cell-transplantation
#1
Howard D Wang, Samuel A J Fidder, Devin T Miller, Georg J Furtmüller, Ali Reza Ahmadi, Felix Nägele, Joseph Lopez, Amy Quan, Joshua Budihardjo, Denver M Lough, Burcu Akpinarli, Joanna 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 (AMR). 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 AMR in VCA. METHODS: Skin transplants from Dark Agouti (DA) to Lewis rats were performed for sensitization...
January 2, 2018: Transplantation
https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#2
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
#3
M Yazawa, H Sasaki, Y Sakurai, H Kudo, R Nakazawa, T Chikaraishi, Y 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 three 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
#4
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
#5
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
#6
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...
November 25, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29165070/bortezomib-in-kidney-transplant-current-use-and-perspectives
#7
Lucio R Requião-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...
November 20, 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
#8
Bassam G Abu Jawdeh, E 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 hasn't 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 3 weekly infusions of SG (320mg/Kg)...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29053910/a-simplified-protocol-using-rituximab-and-immunoglobulin-for-abo-incompatible-low-titre-living-donor-liver-transplantation
#9
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
https://www.readbyqxmd.com/read/28983073/abo-incompatible-renal-transplantation-with-high-antibody-titer-a-case-report
#10
Deepak Shankar Ray, Sharmila Thukral
BACKGROUND Even though renal transplantation across blood groups is not uncommonly practiced nowadays, there is still hesitation regarding ABO-incompatible transplantation with very high baseline antibody titer. In this case report, the outcome of an ABO-incompatible kidney transplant recipient with a high baseline isoagglutinin titer is reported. CASE REPORT The patient was a non-diabetic, 33-year-old man with end-stage renal disease secondary to chronic glomerulonephritis. The only kidney donor available was his mother, who was blood-group incompatible...
October 6, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28960455/nontraditional-sites-for-vascular-anastomoses-to-enable-kidney-transplantation-in-patients-with-major-systemic-venous-thromboses
#11
Bonnie E Lonze, Nabil N Dagher, Nada Alachkar, Annette M Jackson, Robert A Montgomery
Successful renal transplantation requires low-pressure venous drainage to permit adequate outflow from the allograft. We report here a series of three patients in whom the inferior vena cava as well as bilateral iliac veins were thrombosed, making it necessary to explore less traditional vessels for venous drainage of the renal allograft. We utilized the splanchnic vasculature in two cases and the native left renal vein in another. The resulting atypical intra-abdominal locations of these allografts also presented difficulties for arterial anastomoses and for urinary drainage...
December 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28953652/successful-kidney-transplantation-across-a-positive-complement-dependent-cytotoxicity-crossmatch-by-using-c1q-assay-directed-bortezomib-assisted-desensitization-a-case-report
#12
Juhan Lee, Borae G Park, Hyang Sook Jeong, Youn Hee Park, Sinyoung Kim, Beom Seok Kim, Hye Jin Kim, Kyu Ha Huh, Hyeon Joo Jeong, Yu Seun Kim
RATIONALE: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28952921/four-way-kidney-exchange-transplant-with-desensitization-increases-access-to-living-donor-kidney-transplant-first-report-from-india
#13
Vivek B Kute, Himanshu V Patel, Pankaj R Shah, Pranjal R Modi, Veena R Shah, Govind S Kasat, Mayur V Patil, Jaydeep C Patel, Deepak P Kumar, Hargovind L Trivedi
OBJECTIVES: This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. MATERIALS AND METHODS: Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India)...
September 26, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28938311/feasibility-of-monotherapy-by-rituximab-without-additional-desensitization-in-abo-incompatible-living-donor-liver-transplantation
#14
Hidekazu Yamamoto, Koshi Uchida, Seiichi Kawabata, Kaori Isono, Kohei Miura, Shintaro Hayashida, Yuki Oya, Yasuhiko Sugawara, Yukihiro Inomata
BACKGROUND: Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living donor liver transplantation (ABO-i LT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion therapy (LI) were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT...
September 20, 2017: Transplantation
https://www.readbyqxmd.com/read/28929636/risk-factors-for-the-development-of-antibody-mediated-rejection-in-highly-sensitized-pediatric-kidney-transplant-recipients
#15
Irene K Kim, Jua Choi, Ashley Vo, Alexis Kang, Justin Steggerda, Sabrina Louie, Mark Haas, James Mirocha, J Louis Cohen, Helen Pizzo, Elaine S Kamil, Stanley C Jordan, Dechu Puliyanda
ABMR remains a significant concern for early graft loss, especially for those who are HS against HLA antigens. We sought to determine the risk factors leading to ABMR in HS pediatric kidney transplant recipients. From January 2009 to December 2015, 16 HS pediatric kidney transplant patients at our center (age range 2-21) were retrospectively reviewed for outcomes and risk factors for ABMR. All HS patients received desensitization with high-dose IVIG/rituximab prior to transplant. Two groups were examined: ABMR+ (n = 7) and ABMR- (n = 9)...
December 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28838458/successful-simultaneous-pancreas-kidney-re-transplantation-in-a-highly-human-leukocyte-antigen-sensitized-patient
#16
S Kykalos, A Wunsch, T Klein, R Viebahn, P Schenker
BACKGROUND: The waiting time for re-transplantation for sensitized patients is greatly prolonged, given the lack of transplants that are available for this group and additional immunologic barriers. We report the case of a successful re-transplantation in a patient with very high levels of panel reactive antibodies ([PRA] >85%). METHODS: A 45-year-old woman had repetitive rejections after simultaneous pancreas-kidney transplantation, with consequent loss of function of both transplanted organs...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28834181/hospital-readmissions-following-hla-incompatible-live-donor-kidney-transplantation-a-multi-center-study
#17
Babak J Orandi, Xun Luo, Elizabeth A King, Jacqueline M Garonzik-Wang, Sunjae Bae, Robert A Montgomery, Mark D Stegall, Stanley C Jordan, Jose Oberholzer, Ty B Dunn, Lloyd E Ratner, Sandip Kapur, Ronald P Pelletier, John P Roberts, Marc L Melcher, Pooja Singh, Debra L Sudan, Marc P Posner, Jose M El-Amm, Ron Shapiro, Matthew Cooper, George S Lipkowitz, Michael A Rees, Christopher L Marsh, Bashir R Sankari, David A Gerber, Paul W Nelson, Jason Wellen, Adel Bozorgzadeh, A Osama Gaber, Dorry L Segev
Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date...
August 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28792635/favorable-results-in-abo-incompatible-renal-transplantation-without-b-cell-targeted-therapy-advantages-and-disadvantages-of-rituximab-pretreatment
#18
Manabu Okada, Yoshihiko Watarai, Kenta Iwasaki, Kenta Murotani, Kenta Futamura, Takayuki Yamamoto, Takahisa Hiramitsu, Makoto Tsujita, Norihiko Goto, Shunji Narumi, Asami Takeda, Kunio Morozumi, Kazuharu Uchida, Takaaki Kobayashi
The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53)...
August 9, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28774827/therapeutic-apheresis-in-kidney-ab0-incompatible-transplantation
#19
REVIEW
Anna Parolo, Cristina Silvestre, Flavia Neri, Paolo Rigotti, Lucrezia Furian
Desensitization strategies to safely perform ABO incompatible living donor kidney transplantations are various and still evolving. Given the successful outcome of the majority of the approaches, the current trend is focused on a minimization of treatments. Based on this consideration, the evolution at a single Center of the desensitization protocol is herein described. Starting from 2010, 58 AB0 incompatible living donor kidney transplantations were performed at the University-Hospital of Padua. Over the years, the initial desensitization strategy with rituximab single-dose induction, pre-and post-transplant plasmapheresis and CMV-specific immunoglobulin administration has been shifted to a minimized approach, omitting post-transplant antibody removal in 25 cases...
July 10, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28767349/igg-endopeptidase-in-highly-sensitized-patients-undergoing-transplantation
#20
MULTICENTER STUDY
Stanley C Jordan, Tomas Lorant, Jua Choi, Christian Kjellman, Lena Winstedt, Mats Bengtsson, Xiaohai Zhang, Torsten Eich, Mieko Toyoda, Britt-Marie Eriksson, Shili Ge, Alice Peng, Sofia Järnum, Kathryn J Wood, Torbjorn Lundgren, Lars Wennberg, Lars Bäckman, Erik Larsson, Rafael Villicana, Joe Kahwaji, Sabrina Louie, Alexis Kang, Mark Haas, Cynthia Nast, Ashley Vo, Gunnar Tufveson
BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization...
August 3, 2017: New England Journal of Medicine
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