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Chronic antibody rejection

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https://www.readbyqxmd.com/read/28535528/chronic-allograft-injury-an-overview-of-pathogenesis-and-treatment-strategies
#1
Hector M Madariaga, Leonardo V Riella
Chronic allograft injury (CAI) remains one of the biggest challenges in transplantation as it directly affects the long-term allograft survival, an area in which the scientific and transplantation communities have struggled to improve outcomes. Therefore, understanding the mechanisms of CAI is paramount to implement preventive measures and novel therapeutic options. In this review, we will address the latest evidence on CAI, potential etiologies and risk factors including non-adherence, antibody-mediated rejection, recurrence of glomerular disease, BK nephropathy, and calcineurin nephrotoxicity...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#2
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#3
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28506366/antibody-mediated-rejection-after-liver-transplant
#4
REVIEW
Michael Lee
Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy compared with its allograft cohorts of the kidney and lung. Acute AMR is diagnosed based on specific clinical and histopathologic criteria: serum donor specific antibodies, C4d staining, histopathologic findings on liver biopsy, and exclusion of other entities. In contrast, the histologic features of chronic AMR are not as specific and it is a more challenging diagnosis to make. Treatments of acute and chronic AMR include some combination of steroids, immune-modulating agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28489277/pancreas-after-islet-pai-transplantation-in-non-uremic-type-1-diabetes-a-strategy-for-restoring-durable-insulin-independence
#5
S A Wisel, J M Gardner, G R Roll, J Harbell, C E Freise, S Feng, S M Kang, R Hirose, D B Kaufman, A Posselt, P G Stock
Islet transplantation offers a minimally-invasive approach for beta cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet re-infusions from distinct donors, thus increasing the risk for allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the US. However, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28477373/uric-acid-increases-cellular-and-humoral-alloimmunity-in-primary-human-peripheral-blood-mononuclear-cells
#6
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
BACKGROUND: Hyperuricemia is common among kidney transplant recipients and has been associated with worse graft outcome. Since episodes of acute cellular rejection and chronic humoral rejection contribute to decreased graft survival, in this study the effect of uric acid on cellular and humoral alloimmunity was evaluated. METHODS: Cellular alloimmunity was assessed by cell proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC)...
May 5, 2017: Nephrology
https://www.readbyqxmd.com/read/28477360/impact-of-transplant-accessibility-for-sensitized-patients-by-avoiding-unacceptable-antigens
#7
Arnaud Del Bello, Nicolas Congy-Jolivet, Benoit Audry, Corinne Antoine, Laure Esposito, Anne-Laure Hebral, Nassim Kamar
Recent data have confirmed the negative impact of preformed donor-specific antibodies after liver transplantation. In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in liver-transplant recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding preformed DSAs according to several MFI-titer thresholds that have been previously reported to be relevant in liver transplantation. Among the 484 included LT candidates, 99 (20...
May 6, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28465534/low-proportion-of-follicular-regulatory-t-cell-in-renal-transplant-patients-with-chronic-antibody-mediated-rejection
#8
Wen Chen, Jian Bai, Haiyan Huang, Lili Bi, Xiangrui Kong, Yu Gao, Yong Han, Li Xiao, Bingyi Shi
Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465118/development-and-validation-of-a-major-adverse-transplant-event-mate-score-to-predict-late-graft-loss-in-pediatric-heart-transplantation
#9
Christopher S Almond, Helena Hoen, Joseph W Rossano, Chesney Castleberry, Scott R Auerbach, Lingyao Yang, Ashwin K Lal, Melanie D Everitt, Matthew Fenton, Seth A Hollander, Elfriede Pahl, Elizabeth Pruitt, David N Rosenthal, Doff B McElhinney, Kevin P Daly, Manisha Desai
BACKGROUND: There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT. METHODS: Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT...
March 24, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28460546/an-update-on-chemical-pharmacotherapy-options-for-the-prevention-of-kidney-transplant-rejection-with-a-focus-on-costimulation-blockade
#10
Florian Kälble, Matthias Schaier, Sebastian Schäfer, Caner Süsal, Martin Zeier, Claudia Sommerer, Christian Morath
The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28457402/early-vascular-thrombosis-after-kidney-transplantation-can-we-predict-patients-at-risk
#11
R A P de Freitas, M L de Lima, M Mazzali
BACKGROUND: Renal transplant is the therapy of choice for patients with chronic renal disease. In recent years, improvement in immunosuppressive drugs reduced early graft loss associated with acute rejection. However, vascular thrombosis, accounting for 5% of early graft loss, can sensitize the recipient for human leukocyte antibodies, reducing the chance for a second transplant. The aim of this study was to identify risk factors for vascular thrombosis in a single transplant center, to design specific prevention protocol...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28452922/chronic-amr-in-liver-transplant-validation-of-the-1-year-camr-score-s-ability-to-determine-long-term-outcome
#12
Jacqueline G O'Leary, Cory Smith, Juncao Cai, Brent Hart, Linda W Jennings, Matthew Everly, Goran B Klintmalm, Anthony J Demetris
BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has recently predicted 50%10-year death censored allograft loss in patients with Donor Specific Alloantibodies (DSA) Mean Florescence Intensity (MFI) >10 000 and requires confirmation in patients with lower MFI (1000-10 000). METHODS: All patients who underwent liver transplantation (LT) from 1/00-4/09, had DSA (MFI ≥1000) in serum 10-14 months post-LT, and had a protocolized liver biopsy were evaluated (n=230)...
April 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#13
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28445619/mtor-inhibitors-and-risk-for-chronic-antibody-mediated-rejection-after-kidney-transplantation-where-are-we-now
#14
REVIEW
Philippe Grimbert, Olivier Thaunat
Antibody-mediated rejection (AMR) usually starts with generation of donor-specific anti-HLA antibodies (DSA), arising from a B-cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling pathway involved in AMR-related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo. In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dnDSA) or AMR - regardless of the type of regimen - is patient adherence...
April 26, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28444814/chronic-antibody-mediated-rejection-in-nonhuman-primate-renal-allografts-validation-of-human-histological-and-molecular-phenotypes
#15
B A Adam, R N Smith, I A Rosales, M Matsunami, B Afzali, T Oura, A B Cosimi, T Kawai, R B Colvin, M Mengel
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28402253/immunoregulatory-role-of-b-lymphocytes-in-alloresponse-to-kidney-transplant
#16
Tomasz Baran, Maria Boratyńska
B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection...
April 12, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28377770/antibodies-against-apoptotic-cells-present-in-end-stage-lung-disease-patients-do-not-correlate-with-clinical-outcome-after-lung-transplantation
#17
Kevin Budding, Eduard A van de Graaf, Tineke Kardol-Hoefnagel, Erik-Jan D Oudijk, Johanna M Kwakkel-van Erp, C Erik Hack, Henny G Otten
Antibodies against HLA and non-HLA are associated with transplantation outcome. Recently, pretransplant serum IgG antibody levels against apoptotic cells were found to correlate with kidney allograft loss. We investigated the presence of these antibodies in lung transplantation (LTx) patients and evaluated the correlation of pre-LTx serum levels of IgG antibodies against apoptotic cells with LTx outcome. These cells included donor lung endothelial cells (ECs) obtained from lung perfusion fluid collected during LTx procedure...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28373996/not-all-antibodies-are-created-equal-factors-that-influence-antibody-mediated-rejection
#18
REVIEW
Carrie L Butler, Nicole M Valenzuela, Kimberly A Thomas, Elaine F Reed
Consistent with Dr. Paul Terasaki's "humoral theory of rejection" numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR) and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28364323/circulating-and-renal-expression-of-hla-g-prevented-chronic-renal-allograft-dysfunction-in-japanese-recipients
#19
Yuki Okushi, Kazuaki Okino, Kiyotaka Mukai, Yuki Matsui, Norifumi Hayashi, Keiji Fujimoto, Hiroki Adachi, Hideki Yamaya, Hitoshi Yokoyama
BACKGROUND: Although the risk of acute rejection has been studied in renal transplanted patients, there is little data about the long-term renal survival effects of non-classical human leukocyte antigen class I (HLA-G) in Japanese patients. METHOD: We investigated the changes in the estimated glomerular filtration rate (eGFR) for Japanese, and factors affecting the eGFR in 141 adult Japanese subjects whose allografts had survived for at least 1 year. Clinical background data, gender, HLA matching status, the total ischemic time, ABO incompatibility, immunosuppressive therapy, and the serum soluble(s) HLA-G5 level were examined...
March 31, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#20
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig...
May 2017: Gene Therapy
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