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Chronic antibody rejection

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https://www.readbyqxmd.com/read/29146602/donor-specific-and-nonspecific-hla-antibodies-and-outcome-post-lung-transplantation
#1
Stijn E Verleden, Bart M Vanaudenaerde, Marie-Paul Emonds, Dirk E Van Raemdonck, Arne P Neyrinck, Geert M Verleden, Robin Vos
Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are associated with chronic lung allograft dysfunction (CLAD) and mortality post lung transplantation, but data concerning prevalence, time of onset, persistence and effects on long-term outcome remain scarce.We assessed the association between HLA antibodies and CLAD-free and graft survival in a cohort of 362 patients. We stratified our analysis according to DSA status, persistence of antibodies and timing of antibodies (pre-transplant, early or late post-transplant)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#2
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29128017/acute-rejection-and-antibody-mediated-rejection-in-lung-transplantation
#3
REVIEW
Ramsey R Hachem
Despite advances in immunosuppression over the past 25 years, acute cellular rejection remains a common complication early after lung transplantation. Although acute cellular rejection has often not resulted in clinical signs or symptoms of allograft dysfunction, it has been widely recognized as a strong independent risk factor for the development of chronic rejection, emphasizing its clinical significance. In recent years, the role of humoral immunity in lung rejection has been increasingly appreciated, and antibody-mediated rejection is now recognized as a form of rejection that may result in allograft failure...
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29093713/cardiac-non-human-leukocyte-antigen-identification-techniques-and-troubles
#4
REVIEW
Katherine V Gates, Naveen L Pereira, Leigh G Griffiths
Historically efforts have focused on the human leukocyte antigen (HLA) as the major cause for acute and chronic rejection following cardiac transplantation. However, rising evidence indicates that non-HLA antibodies can be both primary initiators and modifiers of antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). The purpose of this review is to assess currently available technologies for non-HLA identification and leveraging such responses toward antibody quantification. Several techniques have been used to identify antigenic determinants of recipient graft-specific non-HLA humoral immune responses, but each comes with its own set of benefits and caveats...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29075627/characteristics-of-donor-specific-antibodies-associated-with-antibody-mediated-rejection-in-lung-transplantation
#5
Antoine Roux, Ines Bendib Le Lan, Sonia Holifanjaniaina, Kimberly A Thomas, Clément Picard, Dominique Grenet, Sandra De Miranda, Benoit Douvry, Laurence Beaumont-Azuar, Edouard Sage, Jérôme Devaquet, Elise Cuquemelle, Morgan Le Guen, Caroline Suberbielle, Chantal Gautreau, Marc Stern, Maura Rossetti, Abdul Monem Hamid, Francois Parquin
Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010-2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMR(Pos), n = 22, and AMR(Neg), n = 83, respectively) were compared...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29061332/human-plasmacytoid-dendritic-cells-acquire-phagocytic-capacity-by-tlr9-ligation-in-the-presence-of-soluble-factors-produced-by-renal-epithelial-cells
#6
Jurjen M Ruben, Gina Stella García-Romo, Eytan Breman, Sandra van der Kooij, Anke Redeker, Ramon Arens, Cees van Kooten
Plasmacytoid dendritic cells (pDCs) are antigen presenting cells specialized in viral recognition through Toll-like receptor (TLR)7 and TLR9, and produce vast amounts of interferon alpha upon ligation of these TLRs. We had previously demonstrated a strong influx of pDCs in the tubulointerstitium of renal biopsies at the time of acute rejection. However, the role of human pDCs in mediating acute or chronic allograft rejection remains elusive. pDCs are thought to have a limited capacity to ingest apoptotic cells, critical for inducing CD4(+) T cell activation via indirect antigen presentation and subsequent activation of antibody producing B cells...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29026877/prolonged-delayed-renal-graft-function-secondary-to-venous-hypertension
#7
Suraj Mishra, Gaurav Gupta, I Moinuddin, Brian Strife, Uma Prasad, D Massey, Anne King, Dhiren Kumar, Chandra S Bhati
The case of a 39-year-old highly sensitized woman who underwent second renal transplantation after being on warfarin because of a history of frequent thromboses of her left femoral arteriovenous graft (AVG) is reported here. The patient received a flow cytometric positive crossmatch kidney transplant from a deceased donor. Her posttransplant course was complicated by prolonged delayed graft function (DGF) lasting for 9 months. Antibody-mediated rejection occurred in the immediate postoperative period. This resolved after treatment, and resolution was confirmed by repeat biopsy...
October 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28992372/the-role-of-c4d-deposition-in-the-diagnosis-of-antibody-mediated-rejection-after-lung-transplantation
#8
P R Aguilar, D Carpenter, J Ritter, R D Yusen, C A Witt, D E Byers, T Mohanakumar, D Kreisel, E P Trulock, R R Hachem
Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs...
October 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28988984/prevention-of-chronic-renal-allograft-rejection-by-as2553627-a-novel-jak-inhibitor-in-a-rat-transplantation-model
#9
Koji Nakamura, Yuka Kawato, Yoko Kaneko, Kaori Hanaoka, Kaori Kubo, Tomonori Nakanishi, Masashi Maeda, Hidehiko Fukahori, Misato Ito, Takahisa Noto, Masamichi Inami, Jun Hirose, Tatsuaki Morokata
BACKGROUND: Janus kinase (JAK) inhibitors are thought to be promising candidates to aid renal transplantation. However, the effectiveness of JAK inhibitors against features of chronic rejection, including interstitial fibrosis/tubular atrophy (IF/TA) and glomerulosclerosis, has not been elucidated. Here, we investigated the effect of AS2553627, a novel JAK inhibitor, on the development of chronic rejection in rat renal transplantation. METHODS: Lewis (LEW) to Brown Norway (BN) rat renal transplantation was performed...
October 5, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28983074/use-of-hepatitis-c-positive-deceased-liver-donors-in-response-to-the-organ-shortage-in-an-endemic-area
#10
Duilio Pagano, Aurelio Seidida, Alessandro Tropea, Giada Pietrosi, Fabrizio di Francesco, Giovanni Battista Vizzini, Angelo Luca, Salvatore Gruttadauria
The region of Sicily, Italy, is witnessing a chronic organ shortage. Thus, to face this critical issue, the use of marginal donors has increased over time. An example of marginal donor expansion is the use of liver donors who are positive for the hepatitis C antibody (HCV+) for HCV+ patients requiring liver transplantation (LT). In view of new advances in HCV therapy, including direct-acting agents (DAAs) to treat HCV in the post-transplant setting, our study focused on a monocentric experience in a series of consecutive LTs performed in adult patients receiving HCV+ liver donor allografts...
October 6, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28969763/peri-and-postsurgical-evaluations-of-renal-transplant
#11
REVIEW
Belkis Erbas
Renal transplantation is the best treatment of choice for patient with chronic renal insufficiency because it provides better quality of life and longer survival. Survival rates for grafts and patients have improved over the recent decades because of significant evolution of surgical techniques and immunosuppressive treatment. However, renal transplantation is still associated with several complications, which may result in poor outcome. Cause of allograft dysfunction, which occurs in the early or late post-transplantation period, should be recognized immediately, so that it can be managed correctly...
November 2017: Seminars in Nuclear Medicine
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/28949089/treatment-of-chronic-antibody-mediated-rejection-with-intravenous-immunoglobulins-and-rituximab-a-multicenter-prospective-randomized-double-blind-clinical-trial
#13
Francesc Moreso, Marta Crespo, Juan C Ruiz, Armando Torres, Alex Gutierrez-Dalmau, Antonio Osuna, Manel Perelló, Julio Pascual, Irina B Torres, Dolores Redondo-Pachón, Emilio Rodrigo, Marcos Lopez-Hoyos, Daniel Seron
There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m(2) and/or severe interstitial fibrosis/tubular atrophy were excluded...
September 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#14
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28933341/c4d-expressing-glomerulopathy-and-proteinuria-post-transplantation-of-a-%C3%A2-too-big-for-size-mismatched-kidney-allograft-an-unusual-case-with-good-outcome%C3%A2
#15
Francois Gougeon, Alexei V Mikhailov, Keisha Gibson, Tomasz Kozlowski, Harsharan K Singh, Volker Nickeleit
A 5-year-old severely growth-retarded child with tubulointerstitial, oliguric end-stage renal disease received an adult-size kidney transplant. Three years post grafting under standard triple immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) de novo nephrotic range proteinuria without the nephrotic syndrome developed. Graft function was normal (serum creatinine: 0.2 - 0.3 mg/dL), there were no donor-specific HLA antibodies (DSA), and the urine sediment was inactive. Two biopsies collected 3 and 4 years post-transplantation showed severe glomerular capillary wall remodeling and associated pseudolinear C4d staining as morphologic correlates for the proteinuria...
September 21, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28926189/environmental-peer-pressure-cd4-t-cell-help-in-tolerance-and-transplantation
#16
REVIEW
Dana Tedesco, Arash Grakoui
The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co-transplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance...
September 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#17
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28911876/immunoglobulin-isotype-switching-of-antibodies-to-vimentin-is-associated-with-development-of-transplant-glomerulopathy-following-human-renal-transplantation
#18
Muthukumar Gunasekaran, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, Jason Wellen, T Mohanakumar
BACKGROUND: Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development...
September 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28906028/graft-outcomes-following-diagnosis-of-post-transplant-lymphoproliferative-disease-in-pediatric-kidney-recipients-a-retrospective-study
#19
Nele K Kanzelmeyer, Britta Maecker-Kolhoff, Henriette Zierhut, Christian Lerch, Murielle Verboom, Dieter Haffner, Lars Pape
Data related to graft outcomes following post-transplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (eight boys) for 3 years after diagnosis of PTLD, with a loss of follow-up after 2 years in two of 12. In all cases, intensity of immunosuppressive therapy was reduced, which switched from calcineurin inhibitor to a mammalian target of rapamycin (mTOR) inhibitor in ten cases. Nine children were treated with six doses of rituximab according to the PED-PTLD-2005 protocol, with additional treatment in one child as per protocol...
September 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28894792/influence-of-hla-matching-on-the-efficacy-of-allogeneic-mesenchymal-stromal-cell-therapies-for-osteoarthritis-and-degenerative-disc-disease
#20
Javier García-Sancho, Ana Sánchez, Aurelio Vega, David C Noriega, Mercedes Nocito
BACKGROUND: The necessity for more effective therapies for chronic osteoarticular diseases has led to the development of treatments based on mesenchymal stem cells (MSCs), the natural precursors of musculoskeletal tissue. Treatments with autologous MSCs yielded excellent results, with nearly 70% improvement of pain and disability in osteoarthritis and degenerative disc disease. Using allogeneic MSCs is logistically more convenient and would widen the pool of eligible patients, but potential immune rejection should be considered...
September 2017: Transplantation Direct
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