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Humoral rejection

Isabella Guzzo, Federica Morolli, Francesca Diomedi Camassei, Antonina Piazza, Elvira Poggi, Luca Dello Strologo
BACKGROUND: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. CASE-DIAGNOSIS/TREATMENT: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d...
October 17, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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
Hanchao Gao, Chengjiang Zhao, Xi Xiang, Yong Li, Yanli Zhao, Zesong Li, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Zhiming Cai, Lisha Mou
Gene-knockout pigs hold great promise as a solution to the shortage of organs from donor animals for xenotransplantation. Several groups have generated gene-knockout pigs via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) and somatic cell nuclear transfer (SCNT). Herein, we adopted a simple and micromanipulator-free method, handmade cloning (HMC) instead of SCNT, to generate double gene-knockout pigs. First, we applied the CRISPR/Cas9 system to target α1,3-galactosyltransferase (GGTA1) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes simultaneously in porcine fetal fibroblast cells (PFFs), which were derived from wild-type Chinese domestic miniature Wuzhishan pigs...
October 8, 2016: Journal of Reproduction and Development
Kelly Lynn Mulvey, Sally B Palmer, Dominic Abrams
Adolescents' evaluations of discriminatory race-based humor and their expectations about peer responses to discrimination were investigated in 8th- (Mage  = 13.80) and 10th-grade (Mage  = 16.11) primarily European-American participants (N = 256). Older adolescents judged race-based humor as more acceptable than did younger adolescents and were less likely to expect peer intervention. Participants who rejected discrimination were more likely to reference welfare/rights and prejudice and to anticipate that peers would intervene...
September 2016: Child Development
Ramiro Fernandez, Stephen Chiu, Kirtee Raparia, Puneet Garcha, Carol Farver, Marie Budev, Anat R Tambur, Malcolm M DeCamp, Scott Budinger, Harris Perlman, T Mohanakumar, Ankit Bharat
A third of lung recipients have preexisting antibodies against nonhuman leukocyte self-antigens (nHAbs) present in the lung tissue. These nHAbs also form de novo in about 70% of patients within 3 years after transplantation. Both preexisting and de novo nHAbs can cause murine lung allograft dysfunction. However, their role in human transplantation remains unclear. We report hyperacute rejection after right lung transplant in a recipient with preexisting nHAbs. The recipient of the left lung from the same donor had an uneventful initial course, but de novo nHAbs developed at 3 weeks, leading to acute humoral rejection...
October 2016: Annals of Thoracic Surgery
Alexander Kroemer, Christopher Cosentino, Jason Kaiser, Cal S Matsumoto, Thomas M Fishbein
Intestinal transplantation is the most immunologically complex of all abdominal organ transplants. Understanding the role both humoral and innate and adaptive cellular immunity play in intestinal transplantation is critical to improving outcomes and increasing indications for patients suffering from intestinal failure. Recent findings highlighting the impact of donor-specific antibodies on intestinal allografts, the role of NOD2 as a key regulator of intestinal immunity, the protective effects of innate lymphoid cells, and the role of Th17 in acute cellular rejection are reviewed here...
November 2016: Current Gastroenterology Reports
Vedran Radojcic, Ivan Maillard
Solid organ and allogeneic hematopoietic cell transplantation have become standard therapeutic interventions that save patient lives and improve quality of life. Our enhanced understanding of transplantation immunobiology has refined clinical management and improved outcomes. However, organ rejection and graft-versus-host disease remain major obstacles to the broader successful application of these therapeutic procedures. Notch signaling regulates multiple aspects of adaptive and innate immunity. Preclinical studies identified Notch signaling as a promising target in autoimmune diseases, as well as after allogeneic hematopoietic cell and solid organ transplantation...
September 8, 2016: Transplantation
Yongkang Wu, Nicole M van Besouw, Yunying Shi, Martin J Hoogduijn, Lanlan Wang, Carla C Baan
Antibody-mediated rejection has emerged as one of the major issues limiting the success of organ transplantation. It exerts a highly negative impact on graft function and outcome, and effective treatment is lacking. The triggers for antibody development, and the mechanisms leading to graft dysfunction and failure, are incompletely understood. The production of antibodies is dependent on instructions from various immunocytes including CD4 T-helper cells that secrete interleukin (IL)-21 and interact with antigen-specific B-cells via costimulatory molecules...
2016: Frontiers in Immunology
X Wei, X Yuan, M Sun, Z Pan, L Hu, L Wang, J He, J Hou
BACKGROUND: C1q-binding donor-specific antibody (DSA) is detrimental to transplanted kidney function. However, the factors that affect C1q binding status are unclear. METHODS: A total of 519 samples from 129 consecutive kidney transplantation patients during 8 years of dynamic follow-up were collected for HLA antibody (Ab) screening and C1q detection. RESULTS: Among the detected HLA Abs, the majority were class II, and the DQ subtypes composed the highest proportion...
July 2016: Transplantation Proceedings
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
Elly Vandermeulen, Stijn E Verleden, Hannelore Bellon, David Ruttens, Elise Lammertyn, Sandra Claes, Jennifer Vandooren, Estafania Ugarte-Berzal, Dominique Schols, Marie-Paule Emonds, Dirk E Van Raemdonck, Ghislain Opdenakker, Geert M Verleden, Robin Vos, Bart M Vanaudenaerde
BACKGROUND: Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD). METHODS: Immunoglobulins (IgA, IgE, IgG1-IgG4, total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n=15) or RAS (n=16) diagnosis; and were compared to stable transplant patients who served as control (n=14)...
September 2016: Transplant Immunology
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Donald Lawrence, David McDermott, Jun Zhou, Scott Rodig, F Stephen Hodi
Immune recognition of tumor targets by specific cytotoxic lymphocytes is essential for the effective rejection of tumors. A phase I clinical trial of ipilimumab (an antibody that blocks CTLA-4 function) in combination with bevacizumab (an antibody that inhibits angiogenesis) in patients with metastatic melanoma found favorable clinical outcomes were associated with increased tumor endothelial activation and lymphocyte infiltration. To better understand the underlying mechanisms, we sought features and factors that changed as a function of treatment in patients...
October 2016: Cancer Immunology Research
Robert P Carroll, Michael Riceman, Christopher M Hope, Anna Zeng, Sue Deayton, Greg D Bennett, P T Coates
Angiotensin II type 1 antibodies (AT1Rab) can mediate antibody mediated rejection (AMR). Pre transplant AT1Rab levels, and risk of rejection were assessed in Kidney Transplant Recipients (KTR) transplanted in our centre from 2013 to 2014 (n=145). 14/145 (9.7%) KTR experienced antibody mediated rejection (AMR). The Hazard Ratio for AMR=3.7 [95% CI 2-26] (p=0.009) for KTR with AT1Rab levels >17.5U/ml. 6/11 of KTR with levels >25U/ml experienced AMR. In 2015 (n=80) KTR were transplanted and 6/80 KTR experienced rejection (2 AMR and 4 TCMR with vascular lesions)...
August 16, 2016: Human Immunology
Xiao-Rui Liu, Yu-Na Guo, Chuan-Mei Qin, Xiao-Li Qin, Fei Tao, Fei Su, Fu-Ju Tian, Yan Zhang, Yi Lin
Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN) can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD) mice but not in the wild-type (WT) mice. To elucidate the molecular mechanisms of differential pregnancy outcomes, differentially expressed genes (DEGs) in the placenta and decidua basalis was revealed by RNA-Seq with CpG ODN or control ODN treatment. Common DEGs in the WT and NOD mice were enriched in antimicrobial/antibacterial humoral responses that may be activated as a primary response to bacterial infection...
2016: International Journal of Molecular Sciences
Elaine Y Cheng, Matthew J Everly, Hugo Kaneku, Nubia Banuelos, Laura J Wozniak, Robert S Venick, Elizabeth A Marcus, Suzanne V McDiarmid, Ronald W Busuttil, Paul I Terasaki, Douglas G Farmer
BACKGROUND: Rejection remains the leading cause of allograft loss, and a major barrier to improving long-term outcomes following intestinal transplantation (ITx). Our aim is to define the prevalence and investigate the role of donor-specific antibody (DSA) on intestinal graft outcomes. METHODS: The study includes 109 transplants performed in 95 recipients at a single center. Patients were screened for DSA pretransplant, monitored regularly posttransplant and when clinically-indicated using the single-antigen bead Luminex assay...
August 3, 2016: Transplantation
Nobuyoshi Hiraoka, Yoshinori Ino, Rie Yamazaki-Itoh
Tertiary lymphoid organs (TLOs) are induced postnatally in non-lymphoid tissues such as those affected by chronic infections, autoimmune diseases, and chronic allograft rejection, and also in cancer tissues. TLOs are thought to provide important lymphocytic functional environments for both cellular and humoral immunity, similar to lymph nodes or Peyer's patches. TLOs have a structure similar to that of lymph nodes or Peyer's patches, including T cell zones, B cell follicles, and high endothelial venules (HEV) without encapsulation...
2016: Frontiers in Immunology
J Rashidi-Alavijeh, A Heinold, K Willuweit, H A Baba, P A Horn, A Paul, O Witzke, G Gerken, K Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins. METHODS: Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay...
July 2016: Zeitschrift Für Gastroenterologie
Beatrice Drexler, Andreas Holbro, Joerg Sigle, Christoph Gassner, Beat M Frey, Stefan Schaub, Patrizia Amico, Alexandra Plattner, Laura Infanti, Thomas Menter, Michael Jörg Mihatsch, Martin Stern, Andreas Buser, Michael Dickenmann
BACKGROUND: The ABO blood group is a major determinant in living donor kidney transplantation since AB antigens are expressed on renal tissue. Little attention has been directed to the ABH-secretor status of the donor kidney. As renal tissue is capable of secreting soluble ABH antigens in secretors, we examined the influence of the ABH-secretor status of kidney donors on outcome in ABO-mismatched living donor kidney transplantation. STUDY DESIGN AND METHODS: We retrospectively analyzed all patients who underwent ABO-mismatched kidney transplantation at the University Hospital Basel from September 2005 to October 2013...
September 2016: Transfusion
Jason M Zimmerer, Phillip H Horne, Mason G Fisher, Thomas A Pham, Keri E Lunsford, Bryce A Ringwald, Christina L Avila, Ginny L Bumgardner
BACKGROUND: The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important because the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney...
September 2016: Transplantation
R Sommaggio, M Uribe-Herranz, M Marquina, C Costa
Transplantation may be the best option for the repair of many cartilage lesions including early osteoarthritis. Currently, autologous and allogeneic chondrocytes are grafted into cartilage defects to treat selected patients with moderate clinical success. However, their limited use justifies exploring novel therapies for cartilage repair. Xenotransplantation could become a solution by offering high cell availability, quality and genetic engineering capabilities. The rejection process of xenogeneic cartilage is thus being elucidated in order to develop counteractive strategies...
2016: European Cells & Materials
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