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Antibody mediated rejection

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https://www.readbyqxmd.com/read/28318622/computer-assisted-topological-analysis-of-renal-allograft-inflammation-adds-to-risk-evaluation-at-diagnosis-of-humoral-rejection
#1
Antoine Sicard, Vannary Meas-Yedid, Maud Rabeyrin, Alice Koenig, Stephanie Ducreux, Frederique Dijoud, Valerie Hervieu, Lionel Badet, Emmanuel Morelon, Jean Christophe Olivo-Marin, Valerie Dubois, Olivier Thaunat
Antibody-mediated rejection is associated with heterogeneous kidney allograft outcomes. Accurate evaluation of risk for graft loss at time of diagnosis is necessary to offer personalized treatment. In contrast with serological and molecular assessment, morpho-histological evaluation of antibody-mediated rejection lesions has not significantly evolved. This relies on Banff classifications designed to be of diagnostic discriminatory power rather than prognostic and face quantitative and qualitative limitations...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28301387/antibody-mediated-rejection-in-heart-transplantation-new-developments-and-old-uncertainties
#2
Valentina Manfredini, Ornella Leone, Valentina Agostini, Luciano Potena
PURPOSE OF REVIEW: Antibody-mediated rejection (AMR) currently represents one of the main problems for clinical management of heart transplant because of its diagnostic complexity and poor evidences supporting treatments. RECENT FINDINGS: Disorder-based diagnosis is a cornerstone in defining AMR. The limitations of the current classification have been partially overcome by novel studies improving the description of the immune-pathological graft abnormalities, and by new molecular approaches allowing a better understanding of the mechanisms behind AMR and of its relationship with cellular rejection and chronic vasculopathy...
March 15, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28297571/prolongation-of-cardiac-allograft-survival-by-endometrial-regenerative-cells-focusing-on-b-cell-responses
#3
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. B-cell activation and antibody levels were determined using fluorescence-activated cell sorting, enzyme-linked immunosorbent assay and ELISpot...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28293239/major-histocompatibility-complex-class-i-chain-related-a-mica-molecules-relevance-in-solid-organ-transplantation
#4
REVIEW
Ajay Kumar Baranwal, Narinder K Mehra
An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28284829/histopathologic-changes-in-anti-angiotensin-ii-type-1-receptor-antibody-positive-kidney-transplant-recipients-with-acute-rejection-and-no-donor-specific-hla-antibodies
#5
Mary Ann Lim, Matthew Palmer, Jennifer Trofe-Clark, Roy Bloom, Annette Jackson, Mary Carmelle Philogene, Malek Kamoun
OBJECTIVE: To determine the association of antibodies against angiotensin II type 1 receptor (AT1R Ab) and histopathologic changes seen in patients with kidney allograft rejection and negative donor specific HLA antibodies (DSA). METHODS: Stored sera from 27 patients who had biopsy-proven rejection in the absence of DSA were tested for AT1R Ab. Biopsy slides of all patients were re-examined and classified according to Banff 2013 criteria. Histopathologic changes were compared between AT1R positive and negative patients...
March 8, 2017: Human Immunology
https://www.readbyqxmd.com/read/28276660/complement-alternative-pathway-deficiency-in-recipients-protects-kidney-allograft-from-ischemia-reperfusion-injury-and-alloreactive-t-cell-response
#6
Federica Casiraghi, Nadia Azzollini, Marta Todeschini, Sonia Fiori, Regiane Aparecida Cavinato, Paola Cassis, Samantha Solini, Francesca Pezzuto, Marilena Mister, Joshua M Thurman, Ariela Benigni, Giuseppe Remuzzi, Marina Noris
Despite the introduction of novel and more targeted immunosuppressive drugs, the long-term survival of kidney transplants has not improved satisfactorily. Early antigen-independent intra-graft inflammation plays a critical role in the initiation of the alloimmune response and impacts long-term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive anti-graft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we wondered whether selective blockade of AP could be a strategy for prolonging kidney graft survival...
March 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28275333/abo-incompatible-living-donor-liver-transplantation-in-focus-of-antibody-rebound
#7
Silke Rummler, Astrid Bauschke, Erik Baerthel, Heike Juette, Katrin Maier, Christina Malessa, Dagmar Barz, Utz Settmacher
BACKGROUND: Living donor liver transplantation (LDLT) is an option to expand the donor organ pool for patients with life-threatening diseases who cannot be supplied with a cadaver organ. Next to the donor risks, complications after ABO-incompatible LDLT (ABOi LDLT) in the recipient are subject to controversial discussion. Improvement in ABOi graft survival rates have been achieved with plasma treatment procedures (PTP) and immunosuppression but antibody-mediated rejection (AMR) and graft loss still occur...
January 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28274484/posttransplant-peripheral-blood-donor-specific-interferon-%C3%AE-enzyme-linked-immune-spot-assay-differentiates-risk-of-subclinical-rejection-and-de-novo-donor-specific-alloantibodies-in-kidney-transplant-recipients
#8
Elena Crespo, Paolo Cravedi, Jaume Martorell, Sergi Luque, Edoardo Melilli, Josep M Cruzado, Marta Jarque, Maria Meneghini, Anna Manonelles, Chiara Donadei, Núria Lloberas, Montse Gomà, Josep M Grinyó, Peter Heeger, Oriol Bestard
Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T-cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T-cell mediated rejection...
March 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28265584/analysis-of-sera-of-recipients-with-allograft-rejection-indicates-that-keratin-1-is-the-target-of-anti-endothelial-antibodies
#9
Xuli Guo, Juan Hu, Weiguang Luo, Qizhi Luo, Jing Guo, Fang Tian, Yingzi Ming, Yizhou Zou
Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28265581/impact-of-desensitization-on-antiviral-immunity-in-hla-sensitized-kidney-transplant-recipients
#10
Mieko Toyoda, Bong-Ha Shin, Shili Ge, James Mirocha, David Thomas, Maggie Chu, Edgar Rodriguez, Christine Chao, Anna Petrosyan, Odette A Galera, Ashley Vo, Jua Choi, Alice Peng, Joseph Kahwaji, Stanley C Jordan
Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28261220/dual-role-of-natural-killer-cells-on-graft-rejection-and-control-of-cytomegalovirus-infection-in-renal-transplantation
#11
REVIEW
Miguel López-Botet, Carlos Vilches, Dolores Redondo-Pachón, Aura Muntasell, Aldi Pupuleku, José Yélamos, Julio Pascual, Marta Crespo
Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28260457/early-versus-late-acute-antibody-mediated-rejection-among-renal-transplant-recipients-in-terms-of-response-to-rituximab-therapy-a-single-center-experience
#12
Osama Gheith, Torki Al-Otaibi, Medhat A Halim, Tarek Mahmoud, Prasad Nair, Mohamed Abdel Monem, Salah Al-Waheeb, Rashad Hassan, Narayanam Nampoory
OBJECTIVES: There are no comparable trials concerning the use of rituximab among renal transplant recipients with acute antibody-mediated rejection. Here, we compared early and late acute antibody-mediated rejection in renal transplant recipients in terms of response to rituximab therapy. MATERIALS AND METHODS: Of 1230 kidney transplants performed at Hamed Al-Essa Organ Transplant Center (Kuwait) over the past 10 years, 103 recipients developed acute antibody-mediated rejections and were subcategorized into 4 groups according to the onset of rejection and rituximab treatment...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28260445/renal-impairment-and-complication-after-kidney-transplant-at-queen-rania-abdulla-children-s-hospital
#13
Reham Issa Almardini, Ghazi Mohamad Salita, Mahdi Qasem Farah, Issa Ahmad Katatbeh, Katibh Al-Rabadi
OBJECTIVES: Kidney transplant is the treatment of choice for end-stage renal disease, but it is not without complications. We review the medical cause of significant renal impairment and complications that developed after kidney transplant in pediatric patients who required hospital admission and intervention and/or who were followed between 2007 and 2016. MATERIALS AND METHODS: A retrospective noninterventional chart review study was conducted in pediatric patients who received a kidney transplant and/or followed at the nephrology clinic at Queen Rania Abdulla Children's Hospital between 2007 and 2016...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28257450/differential-depletion-of-total-t-cells-and-regulatory-t-cells-and-prolonged-allotransplant-survival-in-cd3%C3%A6-humanized-mice-treated-with-polyclonal-anti-human-thymocyte-globulin
#14
Maja Buszko, Benno Cardini, Rupert Oberhuber, Lukas Oberhuber, Bojana Jakic, Anja Beierfuss, Georg Wick, Giuseppe Cappellano
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points...
2017: PloS One
https://www.readbyqxmd.com/read/28255564/endothelial-cells-in-antibody-mediated-rejection-of-kidney-transplantation-pathogenesis-mechanisms-and-therapeutic-implications
#15
REVIEW
Shuo Wang, Chao Zhang, Jina Wang, Cheng Yang, Ming Xu, Ruiming Rong, Tongyu Zhu, Dong Zhu
Antibody-mediated rejection (AMR) has been identified as a main obstacle for stable immune tolerance and long survival of kidney allografts. In spite of new insights into the underlying mechanisms of AMR, accurate diagnosis and efficient treatment are still challenges in clinical practice. Endothelium is the first barrier between recipients' immune systems and grafts in vascularized organ transplants. Considering that endothelial cells express a number of antigens that can be attacked by various allo- and autoantibodies, endothelial cells act as main targets for the recipients' humoral immune responses...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28255562/treatment-of-antibody-mediated-renal-allograft-rejection-improving-step-by-step
#16
Nils Lachmann, Michael Duerr, Constanze Schönemann, Axel Pruß, Klemens Budde, Johannes Waiser
Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR). Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg), low-dose (30 g) intravenous immunoglobulins (IVIG), and plasmapheresis (PPH, 6x) (group RLP, n = 12). Between 2009 and June 2010, patients received bortezomib (1.3 mg/m(2), 4x) together with low-dose IVIG and PPH (group BLP, n = 11)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28255002/antibody-mediated-rejection-due-to-preexisting-versus-de-novo-donor-specific-antibodies-in-kidney-allograft-recipients
#17
Olivier Aubert, Alexandre Loupy, Luis Hidalgo, Jean-Paul Duong van Huyen, Sarah Higgins, Denis Viglietti, Xavier Jouven, Denis Glotz, Christophe Legendre, Carmen Lefaucheur, Philip F Halloran
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205)...
March 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28252564/diffuse-extent-of-peritubular-capillaritis-in-late-antibody-mediated-rejection-associations-with-levels-of-donor-specific-antibodies-and-chronic-allograft-injury
#18
Nicolas Kozakowski, Farsad Eskandary, Harald Herkner, Gregor Bond, Rainer Oberbauer, Heinz Regele, Georg A Böhmig, Željko Kikić
BACKGROUND: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss and while the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate. METHODS: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs...
March 1, 2017: Transplantation
https://www.readbyqxmd.com/read/28251805/effect-of-the-anti-c1s-humanized-antibody-tnt009-and-its-parental-mouse-variant-tnt003-on-hla-antibody-induced-complement-activation-a-preclinical-in-vitro-study
#19
M Wahrmann, J Mühlbacher, L Marinova, H Regele, N Huttary, F Eskandary, G Cohen, G F Fischer, Graham C Parry, J C Gilbert, S Panicker, G A Böhmig
The classical pathway (CP) of complement is believed to significantly contribute to alloantibody-mediated transplant injury, and targeted complement inhibition is currently considered to be a promising approach for preventing rejection. Here, we investigated the mode of action and efficacy of the humanized anti-C1s monoclonal antibody TNT009 and its parental mouse variant, TNT003, in preclinical in vitro models of HLA antibody-triggered CP activation. In flow cytometric assays, we measured the attachment of C1 subcomponents and C4/C3 split products (C4b/d, C3b/d) to HLA antigen-coated flow beads or HLA-mismatched aortic endothelial cells and splenic lymphocytes...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28245084/donor-specificity-but-not-broadness-of-sensitization-is-associated-with-antibody-mediated-rejection-and-graft-loss-in-renal-allograft-recipients
#20
Caroline Wehmeier, Gideon Hönger, Hasret Cun, Patrizia Amico, Patricia Hirt-Minkowski, Argyrios Georgalis, Helmut Hopfer, Michael Dickenmann, Jürg Steiger, Stefan Schaub
Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the 'calculated population-reactive antibodies' (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pre-transplant DSA. 527 consecutive transplantations were divided into four groups: cPRA 0% (n=250), cPRA 1-50% (n=129), cPRA 51-100% (n=43), and DSA (n=105)...
February 28, 2017: American Journal of Transplantation
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