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Humoral rejection

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https://www.readbyqxmd.com/read/27870356/clinical-and-immunological-relevance-of-antibodies-in-solid-organ-transplantation
#1
REVIEW
N K Mehra, A K Baranwal
The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection...
December 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27866926/evaluation-of-humoral-immunity-profiles-to-identify-heart-recipients-at-risk-for-development-of-severe-infections-a-multicenter-prospective-study
#2
Elizabeth Sarmiento, Maria Jaramillo, Leticia Calahorra, Juan Fernandez-Yañez, Miguel Gomez-Sanchez, Maria G Crespo-Leiro, Maria Paniagua, Luis Almenar, Monica Cebrian, Gregorio Rabago, Beltran Levy, Javier Segovia, Manuel Gomez-Bueno, Javier Lopez, Sonia Mirabet, Joaquin Navarro, Juan Jose Rodriguez-Molina, Eduardo Fernandez-Cruz, Javier Carbone
BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV)...
October 17, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27830476/production-of-heterozygous-alpha-1-3-galactosyltransferase-ggta1-knock-out-transgenic-miniature-pigs-expressing-human-cd39
#3
Kimyung Choi, Joohyun Shim, Nayoung Ko, Heejong Eom, Jiho Kim, Jeong-Woong Lee, Dong-Il Jin, Hyunil Kim
Production of transgenic pigs for use as xenotransplant donors is a solution to the severe shortage of human organs for transplantation. The first barrier to successful xenotransplantation is hyperacute rejection, a rapid, massive humoral immune response directed against the pig carbohydrate GGTA1 epitope. Platelet activation, adherence, and clumping, all major features of thrombotic microangiopathy, are inevitable results of immune-mediated transplant rejection. Human CD39 rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator...
November 9, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27826340/role-of-soluble-st2-as-a-marker-for-rejection-after-heart-transplant
#4
Ga Yeon Lee, Jin-Oh Choi, Eun-Seon Ju, Yoo-Jung Lee, Eun-Seok Jeon
BACKGROUND AND OBJECTIVES: Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. SUBJECTS AND METHODS: A total of 494 blood samples acquired at the time of endomyocardial biopsy were analyzed in 67 HTx cases from September 2006 to August 2014...
November 2016: Korean Circulation Journal
https://www.readbyqxmd.com/read/27822209/antibody-subclass-repertoire-and-graft-outcome-following-solid-organ-transplantation
#5
REVIEW
Nicole M Valenzuela, Michelle J Hickey, Elaine F Reed
Long-term outcomes in solid organ transplantation are constrained by the development of donor-specific alloantibodies (DSA) against human leukocyte antigen (HLA) and other targets, which elicit antibody-mediated rejection (ABMR). However, antibody-mediated graft injury represents a broad continuum, from extensive complement activation and tissue damage compromising the function of the transplanted organ, to histological manifestations of endothelial cell injury and mononuclear cell infiltration but without concurrent allograft dysfunction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27821629/polyomavirus-reactivation-and-immune-responses-to-kidney-specific-self-antigens-in-transplantation
#6
Michael E Seifert, Muthukumar Gunasekaran, Timothy A Horwedel, Reem Daloul, Gregory A Storch, Thalachallour Mohanakumar, Daniel C Brennan
Humoral immune responses against donor antigens are important determinants of long-term transplant outcomes. Reactivation of the polyomavirus BK has been associated with de novo antibodies against mismatched donor HLA antigens in kidney transplantation. The effect of polyomavirus reactivation (BK viremia or JC viruria) on antibodies to kidney-specific self-antigens is unknown. We previously reported excellent 5-year outcomes after minimization of immunosuppression for BK viremia and after no intervention for JC viruria...
November 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27818660/unraveling-the-role-of-allo-antibodies-and-transplant-injury
#7
REVIEW
Yoshiko Matsuda, Minnie M Sarwal
Alloimmunity driving rejection in the context of solid organ transplantation can be grossly divided into mechanisms predominantly driven by either T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), though the co-existence of both types of rejections can be seen in a variable number of sampled grafts. Acute TCMR can generally be well controlled by the establishment of effective immunosuppression (1, 2). Acute ABMR is a low frequency finding in the current era of blood group and HLA donor/recipient matching and the avoidance of engraftment in the context of high-titer, preformed donor-specific antibodies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27805521/smoking-is-related-to-postoperative-pulmonary-complications-and-graft-outcomes-in-renal-transplant-patients
#8
Balam Er Dedekargınoğlu, Gaye Ulubay, Elif Küpeli, Mahir Kırnap, Füsun Öner Eyüboğlu, Mehmet Haberal
OBJECTIVES: Renal transplant is an important treatment option for end-stage renal disease. A successful kidney transplant improves the quality of life and reduces the mortality risk compared with maintenance dialysis in patients with end-stage renal disease. Several immunologic and nonimmunologic factors are responsible for graft outcomes in renal transplant patients. Our study was performed to evaluate the role of smoking on postoperative pulmonary complications and graft outcomes in renal transplant patients...
November 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27798373/prolongation-of-cardiac-allograft-survival-by-endometrial-regenerative-cells-focusing-on-b-cell-responses
#9
Xiaoxi Xu, Xiaochun Li, Xiangying Gu, Bai Zhang, Weijun Tian, Hongqiu Han, Peng Sun, Caigan Du, Hao Wang
: : Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2(b)) donor mice and BALB/c (H-2(d)) recipients...
October 26, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27752765/acute-kidney-transplant-rejection-mediated-by-angiotensin-ii-type-1-receptor-antibodies-in-a-pediatric-hyperimmune-patient
#10
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...
January 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27742824/renal-transplantation-in-sensitized-children-and-young-adults-a-nationwide-approach
#11
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
https://www.readbyqxmd.com/read/27725344/production-of-%C3%AE-1-3-galactosyltransferase-and-cytidine-monophosphate-n-acetylneuraminic-acid-hydroxylase-gene-double-deficient-pigs-by-crispr-cas9-and-handmade-cloning
#12
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
https://www.readbyqxmd.com/read/27684393/race-based-humor-and-peer-group-dynamics-in-adolescence-bystander-intervention-and-social-exclusion
#13
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
https://www.readbyqxmd.com/read/27645977/humoral-human-lung-allograft-rejection-by-tissue-restricted-non-hla-antibodies
#14
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
https://www.readbyqxmd.com/read/27645751/intestinal-transplant-inflammation-the-third-inflammatory-bowel-disease
#15
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
https://www.readbyqxmd.com/read/27607530/notch-signaling-and-alloreactivity
#16
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...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27602031/the-biological-effects-of-il-21-signaling-on-b-cell-mediated-responses-in-organ-transplantation
#17
REVIEW
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
https://www.readbyqxmd.com/read/27569927/association-of-c1q-binding-status-with-de-novo-hla-antibody-clinical-features-and-allograft-function-in-kidney-transplantation-patients-during-eight-years-of-dynamic-follow-up
#18
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
https://www.readbyqxmd.com/read/27563301/antibody-dependent-nk-cell-activation-is-associated-with-late-kidney-allograft-dysfunction-and-the-complement-independent-alloreactive-potential-of-donor-specific-antibodies
#19
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
https://www.readbyqxmd.com/read/27561239/humoral-immunity-in-phenotypes-of-chronic-lung-allograft-dysfunction-a-broncho-alveolar-lavage-fluid-analysis
#20
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
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