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Chronic antibody rejection

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https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#1
REVIEW
Daniel J Firl, Gilles Benichou, James I Kim, Heidi Yeh
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#2
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#3
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28187998/a-systematic-review-of-the-use-of-rituximab-for-the-treatment-of-antibody-mediated-renal-transplant-rejection
#4
REVIEW
Philip S Macklin, Peter J Morris, Simon R Knight
Rituximab is a B-lymphocyte depleting agent that is used to treat hematological malignancies and autoimmune diseases. Recently, it has gained interest as an immunomodulatory agent in renal transplantation. This systematic review evaluates the evidence for its use in the treatment of acute and chronic antibody-mediated renal transplant rejection (AAMR; CAMR). A systematic search of four databases and three trial registries was conducted. The small number and heterogeneous nature of included studies precluded meta-analysis and thus a narrative review was conducted...
January 24, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#5
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#6
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28151033/graft-immunocomplex-capture-fluorescence-analysis-to-detect-donor-specific-antibodies-and-hla-antigen-complexes-in-the-allograft
#7
Tsukasa Nakamura, Hidetaka Ushigome, Kiyoko Watabe, Yui Imanishi, Koji Masuda, Takehisa Matsuyama, Shumpei Harada, Katsuhiro Koshino, Taku Iida, Shuji Nobori, Norio Yoshimura
BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) is an attractive method to detect donor-specific anti-HLA antibodies (DSA) and HLA antigen complexes. Currently, antibody-mediated rejection (AMR) due to DSA is usually diagnosed by C4d deposition and serological DSA detection. Conversely, there is a discrepancy between these findings frequently. Thereupon, our graft ICFA technique may contribute to establish the diagnosis of AMR. METHODS: Graft samples were obtained by a percutaneous needle biopsy...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28148598/gene-expression-profiling-for-the-identification-and-classification-of-antibody-mediated-heart-rejection
#8
Alexandre Loupy, Jean Paul Duong Van Huyen, Luis Hidalgo, Jeff Reeve, Maud Racapé, Olivier Aubert, Jeffery M Venner, Konrad Falmuski, Marie-Cécile Bories, Thibaut Beauscart, Romain Guillemain, Arnaud François, Sabine Pattier, Claire Toquet, Arnaud Gay, Philippe Rouvier, Shaida Varnous, Pascal Leprince, Jean-Philippe Empana, Carmen Lefaucheur, Patrick Bruneval, Xavier Jouven, Philip F Halloran
BACKGROUND: -Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains regarding the pathophysiology of AMR and how detection of immune activity, injury degree and stage could be improved by intragraft gene expression profiling. METHODS: -We prospectively monitored 617 heart transplant recipients referred from four French transplant centers (January 1st 2006 - January 1st 2011) for AMR. We compared patients with AMR (n=55) to a matched control group of 55 patients without AMR...
February 1, 2017: Circulation
https://www.readbyqxmd.com/read/28135784/morphologic-patterns-and-treatment-of-transplant-glomerulopathy-a-retrospective-analysis
#9
Rui Abreu, Fernanda Carvalho, Helena Viana, Isabel Mesquita, Marília Possante, Inês Aires, Fernando Caeiro, Cecília Silva, Patrícia Cotovio, Aníbal Ferreira, Francisco Remédio, Fernando Nolasco
Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7.1 (3.6-11.8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10...
January 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28127571/desensitization-overcoming-the-immunologic-barriers-to-transplantation
#10
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
#11
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/28109026/refinement-of-the-criteria-for-ultrastructural-peritubular-capillary-basement-membrane-multilayering-in-the-diagnosis-of-chronic-active-acute-antibody-mediated-rejection
#12
Heounjeong Go, Sung Shin, Young Hoon Kim, Duck Jong Han, Yong Mee Cho
Chronic active/acute antibody-mediated rejection (cABMR) is the main cause of late renal allograft loss. Severe peritubular capillary basement membrane multilayering (PTCML) assessed on electron microscopy is one diagnostic feature of cABMR according to the Banff2013 classification. We aimed to refine the PTCML criteria for an earlier diagnosis of cABMR. We retrospectively investigated ultrastructural features of 159 consecutive renal allografts and 44 non-allografts. The presence of serum donor-specific antibodies at the time of biopsy of allografts was also examined...
January 21, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28104165/highly-immunogenic-dqb1-mismatch-eplets-are-associated-with-development-of-chronic-active-antibody-mediated-rejection-a-first-report-from-japan
#13
D Iwami, K Hotta, H Sasaki, T Hirose, H Higuchi, Y Takada, N Shinohara
BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28092129/bortezomib-in-the-treatment-of-antibody-mediated-rejection-in-pediatric-kidney-transplant-recipients-a-multicenter-midwest-pediatric-nephrology-consortium-study
#14
Sarah Kizilbash, Donna Claes, Isa Ashoor, Ashton Chen, Sara Jandeska, Raed Bou Matar, Jason Misurac, Joseph Sherbotie, Katherine Twombley, Priya Verghese
Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients...
January 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#15
Rachel Hogen, Joseph DiNorcia, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress...
January 3, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#16
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#17
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/28009780/kidney-transplant-with-low-levels-of-dsa-or-low-positive-b-flow-crossmatch-an-underappreciated-option-for-highly-sensitized-transplant-candidates
#18
Carrie Schinstock, Manish Gandhi, Wisit Cheungpasitporn, Donald Mitema, Mikel Prieto, Patrick Dean, Lynn Cornell, Fernando Cosio, Mark Stegall
BACKGROUND: Avoiding donor specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed. METHODS: We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low+XM, +DSA/high+XM, and -DSA/+XM and followed for a mean of 4.1±1...
December 22, 2016: Transplantation
https://www.readbyqxmd.com/read/28005572/polyreactive-natural-antibodies-in-transplantation
#19
Emmanuel Zorn, Sarah B See
PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27995324/hla-epitope-matching-in-pediatric-renal-transplantation
#20
Matthew P Sypek, Peter Hughes, Joshua Y Kausman
Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications...
December 19, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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