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Donor specific antibodies

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https://www.readbyqxmd.com/read/29046806/development-of-a-fully-automated-chemiluminescence-immunoassay-for-urine-monomeric-laminin-%C3%AE-2-as-a-promising-diagnostic-tool-of-non-muscle-invasive-bladder-cancer
#1
Masatoshi Nakagawa, Takashi Karashima, Masayuki Kamada, Eisaku Yoshida, Toru Yoshimura, Masanori Nojima, Keiji Inoue, Taro Shuin, Motoharu Seiki, Naohiko Koshikawa
BACKGROUND: Monomeric laminin-γ2 in urine is a potential biomarker for bladder cancer. However, the current detection system uses an antibody that cannot discriminate between monomeric laminin-γ2 and the heterotrimeric γ2 chain of laminin-332, which may cause false-positive reactions. The present study aimed to develop a fully automated chemiluminescence immunoassay system using a specific monoclonal antibody against monomeric laminin-γ2. METHODS: In total, 237 urine specimens (84 from patients with bladder cancer, 48 from patients with benign urological disease, and 105 from healthy donors) were collected, and monomeric laminin-γ2 values in the urine were measured using a fully automated chemiluminescence immunoassay...
2017: Biomarker Research
https://www.readbyqxmd.com/read/29045076/outside-in-hla-class-i-signaling-regulates-icam-1-clustering-and-endothelial-monocyte-interactions-via-mtor-in-transplant-antibody-mediated-rejection
#2
Sahar Salehi, Rebecca A Sosa, Yi-Ping Jin, Shoichi Kageyama, Michael C Fishbein, Enrique Rozengurt, Jerzy W Kupiec-Weglinski, Elaine F Reed
Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment...
October 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29042457/neutralizing-antibody-mediated-response-and-risk-of-bk-virus-associated-nephropathy
#3
Morgane Solis, Aurélie Velay, Raphaël Porcher, Pilar Domingo-Calap, Eric Soulier, Mélanie Joly, Mariam Meddeb, Wallys Kack-Kack, Bruno Moulin, Siamak Bahram, Françoise Stoll-Keller, Heidi Barth, Sophie Caillard, Samira Fafi-Kremer
BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype-specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#4
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29039101/methods-for-analysis-of-nanoparticle-immunosuppressive-properties-in-vitro-and-in-vivo
#5
Timothy M Potter, Barry W Neun, Marina A Dobrovolskaia
Adverse drug effects on the immune system function represent a significant concern in the pharmaceutical industry, because 10-20% of the drug withdrawal from the market is accounted to immunotoxicity. Immunosuppression is one such adverse effect. The traditional immune function test used to estimate materials' immunosuppression is a T-cell-dependent antibody response (TDAR). This method involves a 28 day in vivo study evaluating the animal's antibody titer to a known antigen (KLH) with and without challenge...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29037595/cellular-characterization-of-optical-coherence-tomography-and-outer-retinal-bands-using-specific-immunohistochemistry-markers-and-clinical-implications
#6
Nicolás Cuenca, Isabel Ortuño-Lizarán, Isabel Pinilla
PURPOSE: Optical coherence tomography has been a technological breakthrough in the diagnosis, treatment, and follow-up of many ocular diseases, especially retinal and neuro-ophthalmologic pathologic conditions. Until now, several controversies have arisen over the specific cell types that the bands observed in the OCT represent, especially over the 4 outer retinal bands. DESIGN: To correlate the 4 outer hyperreflective bands observed in the OCT with the histologic structures using human retinal sections and immunocytochemistry at the fovea level...
October 13, 2017: Ophthalmology
https://www.readbyqxmd.com/read/29032062/virus-specific-t-cells-broadening-applicability
#7
REVIEW
A John Barrett, Susan Prockop, Catherine M Bollard
Virus infection still remains an appreciable cause of morbidity and mortality after Hematopoietic stem cell transplant (HSCT). While pharmacotherapy and/or antibody therapy may help to prevent or treat viral disease, these drugs are expensive, toxic and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (e.g. Ad and BKV), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplant without causing GvHD...
October 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29027535/transplant-glomerulopathy
#8
REVIEW
Edward J Filippone, Peter A McCue, John L Farber
In the renal allograft, transplant glomerulopathy represents a morphologic lesion and not a specific diagnosis. The hallmark pathologic feature is glomerular basement membrane reduplication by light microscopy or electron microscopy in the absence of immune complex deposits. Transplant glomerulopathy results from chronic, recurring endothelial cell injury that can be mediated by HLA alloantibodies (donor-specific antibodies), various autoantibodies, cell-mediated immune injury, thrombotic microangiopathy, or chronic hepatitis C...
October 13, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29026463/t-cell-allorecognition-of-donor-glutathione-s-transferase-t1-in-plasma-cell-rich-rejection
#9
María José Martínez-Bravo, Berta Sánchez, José Manuel Sousa, María José Acevedo, Miguel Angel Gómez-Bravo, Antonio Núñez-Roldán, Isabel Aguilera
AIM: To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1 (GSTT1) alleles (don+/rec-), and 4 were matched (don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection (former de novo immune hepatitis)...
September 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/29024716/accelerated-humoral-renal-allograft-rejection-due-to-hla-c14-mediated-allosensitization-to-hla-bw6
#10
Stephen P Persaud, Brian Duffy, Donna L Phelan, Thalachallour Mohanakumar, Rowena Delos Santos, Joseph P Gaut, Chang Liu
OBJECTIVES: To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera. METHODS: Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods...
October 9, 2017: Human Immunology
https://www.readbyqxmd.com/read/28990779/designer-%C3%AE-1-6-fucosidase-mutants-enable-direct-core-fucosylation-of-intact-n-glycopeptides-and-n-glycoproteins
#11
Chao Li, Shilei Zhu, Christopher Ma, Lai-Xi Wang
Core fucosylation of N-glycoproteins plays a crucial role in modulating the biological functions of glycoproteins. Yet, the synthesis of structurally well-defined, core-fucosylated glycoproteins remains a challenging task due to the complexity in multi-step chemical synthesis or the inability of the biosynthetic α1,6-fucosyltransferase (FUT8) to directly fucosylate full-size mature N-glycans in a chemoenzymatic approach. We report in this paper the design and generation of potential α1,6-fucosynthase and fucoligase for direct core-fucosylation of intact N-glycoproteins...
October 9, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28988984/prevention-of-chronic-renal-allograft-rejection-by-as2553627-a-novel-jak-inhibitor-in-a-rat-transplantation-model
#12
Koji Nakamura, Yuka Kawato, Yoko Kaneko, Kaori Hanaoka, Kaori Kubo, Tomonori Nakanishi, Masashi Maeda, Hidehiko Fukahori, Misato Ito, Takahisa Noto, Masamichi Inami, Jun Hirose, Tatsuaki Morokata
BACKGROUND: Janus kinase (JAK) inhibitors are thought to be promising candidates to aid renal transplantation. However, the effectiveness of JAK inhibitors against features of chronic rejection, including interstitial fibrosis/tubular atrophy (IF/TA) and glomerulosclerosis, has not been elucidated. Here, we investigated the effect of AS2553627, a novel JAK inhibitor, on the development of chronic rejection in rat renal transplantation. METHODS: Lewis (LEW) to Brown Norway (BN) rat renal transplantation was performed...
October 5, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#13
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28979262/cd28-blockade-ex-vivo-induces-alloantigen-specific-immune-tolerance-but-preserves-t-cell-pathogen-reactivity
#14
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28974434/graft-immunologic-events-in-deceased-donor-kidney-transplant-recipients-with-preformed-hla-donor-specific-antibodies
#15
Xicohténcatl Ixtlapale-Carmona, Adriana Arvizu, Adrian De-Santiago, Norma González-Tableros, Mayra López, Natalia Castelán, Lluvia A Marino, Norma O Uribe-Uribe, Alan G Contreras, Mario Vilatobá, Luis E Morales-Buenrostro, Josefina Alberú
INTRODUCTION: Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center...
September 30, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28970687/detection-of-t-and-b-cells-specific-complement-fixing-alloantibodies-using-flow-cytometry-a-diagnostic-approach-for-a-resource-limited-laboratory
#16
Dharmendra Jain, Pranav Dorwal, Amit Pande, Neetu Tyagi, Simmi Mehra, Vimarsh Raina
BACKGROUND AND OBJECTIVES: Various methods have been reported for the detection of antibodies in recipient sera, which can be human leukocyte antigens (HLAs) or non-HLA specific, complement- or noncomplement fixing, as well as donor T (HLA-Class-I) and/or B cell (HLA-Class-I and II) specific. These alloantibodies play a pivotal role in antibody-mediated renal transplantation rejection. Deposition of C4d in peritubular capillaries of a kidney biopsy is a marker of antibody-mediated rejection...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28970678/inra-a-new-high-frequency-antigen-in-the-indian-in023-blood-group-system
#17
Sanmukh R Joshi, Ankita Sheladiya, Kinjal V Mendapara-Dobariya
BACKGROUND: The INDIAN blood group system comprises 4 antigens sensitive to enzymes and 2-aminoethyl isothiouronium bromide (AET). AIM: The patient's antibody was investigated for its specificity to the high-frequency antigens (HFA) of this system. MATERIAL AND METHODS: Low ionic strength solution (LISS)-tube/LISS-indirect antiglobulin test (IAT) methods were used. The patient's red blood cells (RBCs) were tested with antisera to HFA. Her antibody was tested with RBCs lacking the HFA...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28968970/identification-of-a-novel-hiv-1-neutralizing-antibody-from-a-crf07_bc-infected-chinese-donor
#18
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, Yuxian He
The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965920/selection-and-validation-of-antibody-clones-against-igg-and-iga-subclasses-in-switched-memory-b-cells-and-plasma-cells
#19
Elena Blanco, Martin Perez-Andres, Luzalba Sanoja-Flores, Marjolein Wentink, Ondrej Pelak, Marta Martín-Ayuso, Georgiana Grigore, Juan Torres-Cañizales, Eduardo López-Granados, Tomas Kalina, Mirjam Van der Burg, Sonia Arriba-Méndez, Santiago Santa Cruz, Noemí Puig, Jacques J M van Dongen, Alberto Orfao
The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, but except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry...
September 28, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28958895/young-female-donors-do-not-increase-risk-of-gvhd-or-impact-overall-outcomes-in-pediatric-hla-matched-sibling-hsct
#20
Paola Friedrich, Pilar Guerra-Garcia, Alyssa Stetson, Christine Duncan, Leslie Lehmann
Optimal donor selection is critical in hematopoietic stem-cell transplantation (HSCT). Donor/recipient sex-mismatch, donor age and female donor/donor parity are known to impact graft-versus-host disease (GVHD) and outcomes in adults. Minor histocompatibility antigens (mHCA) encoded by the human Y-chromosome (H-Y) can result in specific antibody formation in some female donors, may increase in frequency with increasing donor age and may be contributory to the increased incidence of GVHD. To better understand the role of donor age/sex and sex matching in HSCT outcomes, we conducted a retrospective study of pediatric patients receiving their first myeloablative sibling-donor HSCT (n=244) from 1998 to 2012...
September 25, 2017: Biology of Blood and Marrow Transplantation
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