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Transplant antibody desensitization

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
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 ( and Embase ( using different associations of the following keywords (MESH): "allogenic response; allograft; immunosuppression; ABO incompatible transplantation; donor specific antibodies; HLA incompatible; desensitization; kidney transplantation"...
September 23, 2016: Progrès en Urologie
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
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...
September 1, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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
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
Joseph Kahwaji, Stanley C Jordan, Reiad Najjar, Patarapha Wongsaroj, Jua Choi, Alice Peng, Rafael Villicana, Ashley Vo
BACKGROUND: 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. METHODS: Living donor kidney transplants that took place between July 2006 and December 2010 were considered retrospectively...
August 16, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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
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)
David Shaffer, Irene D Feurer, Deborah Crowe, Heidi Schaefer
BACKGROUND: Desensitization with IVIG and rituximab allows acceptable graft survival in sensitized kidney transplant recipients with preexisting donor-specific antibodies (DSAs) and a positive crossmatch. There is little published data reporting the durability of DSA removal in kidney transplant recipients treated with IVIG and rituximab. METHODS: We conducted a 3-year prospective DSA monitoring study in living donor kidney recipients with preexisting DSA to assess the durability of DSA removal after a perioperative protocol of IVIG and rituximab...
February 2016: Transplantation Direct
Irene K Kim, Jua Choi, Ashley A Vo, Alexis Kang, Mitasha Patel, Mieko Toyoda, James Mirocha, Elaine S Kamil, J Louis Cohen, Sabrina Louie, Odette Galera, Stanley C Jordan, Dechu P Puliyanda
BACKGROUND: Studies show that alemtuzumab, a potent lymphocyte-depleting agent, is well tolerated in pediatric renal transplantation. We report on the use of alemtuzumab induction in highly HLA sensitized (HS) pediatric kidney transplant patients. METHODS: 50 pediatric renal transplants were performed from 1/2009-12/2014. 15 HS patients received IVIG (2gm/kg x2 doses) /rituximab (375mg/m x1) for desensitization with alemtuzumab induction (15-30mg, 1 dose, subcutaneous), while 35 nonsensitized patients received anti-IL-2R...
August 5, 2016: Transplantation
Emmanuel A Fadeyi, Robert J Stratta, Alan C Farney, Gregory J Pomper
OBJECTIVES: Transplantation of the blood group A2B in a recipient was successfully performed in the setting of receiving a deceased donor kidney from an "incompatible" A1B donor. METHODS: The donor and recipient were both typed for ABO blood group, including ABO genotyping. The donor and recipient were tested for ABO, non-ABO, and human leukocyte antigen (HLA) antibodies. The donor and recipient were typed for HLA antigens, including T- and B-flow cytometry crossmatch tests...
August 2016: American Journal of Clinical Pathology
Jelena Stojanovic, Anna Adamusiak, Nicos Kessaris, Pankaj Chandak, Zubir Ahmed, Neil J Sebire, Grainne Walsh, Helen E Jones, Stephen D Marks, Nizam Mamode
BACKGROUND: Blood group incompatible transplantation (ABOi) in children is rare as pretransplant conditioning remains challenging and concerns persist about the potential increased risk of rejection. METHODS: We describe the results of 11 ABOi pediatric renal transplant recipients in the 2 largest centers in the United Kingdom, sharing the same tailored desensitization protocol. Patients with pretransplant titers of 1 or more in 8 received rituximab 1 month before transplant; tacrolimus and mycophenolate mofetil were started 1 week before surgery...
July 12, 2016: Transplantation
Masaki Honda, Seisuke Sakamoto, Rieko Sakamoto, Shirou Matsumoto, Tomoaki Irie, Koushi Uchida, Keita Shimata, Seiichi Kawabata, Kaori Isono, Shintaro Hayashida, Hidekazu Yamamoto, Fumio Endo, Yukihiro Inomata
We herein present the case of a four-yr-old boy with PA who developed AMR after ABO-incompatible LDLT despite undergoing B cell desensitization using rituximab. Although the CD19+ lymphocyte count decreased to 0.1% nine days after the administration of rituximab, he developed a high fever which was accompanied by arthralgia due to a streptococcal infection 13 days after rituximab prophylaxis. After the clearance of the infection, he underwent ABO-incompatible LDLT 36 days after the administration of rituximab...
September 2016: Pediatric Transplantation
Kosuke Masutani, Akihiro Tsuchimoto, Kei Kurihara, Yasuhiro Okabe, Hidehisa Kitada, Masayoshi Okumi, Kazunari Tanabe, Masafumi Nakamura, Takanari Kitazono, Kazuhiko Tsuruya
BACKGROUND: ABO-incompatible (ABO-I) kidney transplantation (KTx) is an established procedure to expand living donor sources. Although graft and patient survival rates are comparable between ABO-compatible (ABO-C) and ABO-I KTx, several studies have suggested that ABO-I KTx is associated with infection. Additionally, the histological findings and incidence of antibody-mediated rejection under desensitization with rituximab and plasmapheresis remain unclear. METHODS: We reviewed 327 patients who underwent living-donor KTx without preformed donor-specific antibodies (ABO-C, n = 226; ABO-I, n = 101)...
July 7, 2016: Transplantation
Manuel A Moreno Gonzales, Manish J Gandhi, Carrie A Schinstock, Natalie A Moore, Byron H Smith, Nong Y Braaten, Mark D Stegall
BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events...
July 1, 2016: Transplantation
J D Kim, D L Choi, S-G Kim, A-J Lee
The outcomes of patients who undergo ABO-incompatible (ABO-I) living-donor liver transplantation (LDLT) have markedly improved as strategies have become more innovative and advanced. Here, we describe 25 cases of ABO-I LDLT with a simplified protocol and compare the outcomes to those of ABO-compatible LDLT. We analyzed outcomes via a retrospective review of 182 adult LDLT cases including 25 ABO-I LDLTs from January 2011 to December 2014. Propensity scoring was used to compare the groups. The desensitization protocol included plasma exchange, rituximab, and intravenous immunoglobulin without local infusion therapy...
May 2016: Transplantation Proceedings
Nizam Mamode, Stephen D Marks
Desensitization protocols should be considered for children with positive crossmatches awaiting renal transplantation. Children are sensitized usually due to previous renal (and/or other solid-organ) transplants but can be from administration of blood and/or platelet transfusions, infections, and immunizations (as sensitization from pregnancy is a rare occurrence in pediatric patients). However, the definition of HLA-incompatible (HLAi) renal transplantation in the literature varies and is best considered only when there is a positive cross-match (positive baseline flow cytometric cross-match or positive complement-dependent cytotoxic cross-match)...
October 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Anat R Tambur, Denis Glotz, Nancy D Herrera, Erik N Chatroop, Tal Roitberg, John J Friedewald, David Gjertson
Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment...
August 2016: Human Immunology
Pernille Koefoed-Nielsen, Claus Bistrup, Mette Christiansen
Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers...
June 3, 2016: Journal of Clinical Apheresis
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