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Donor specific antibodies

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https://www.readbyqxmd.com/read/28647211/tubuloreticular-inclusions-in-peritubular-capillaries-of-renal-allografts
#1
Jee Youn Lee, Seung Hwan Song, Yu Seun Kim, Beom Jin Lim, Soon Il Kim, Myoung Soo Kim, Hyeon Joo Jeong
BACKGROUND: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. METHODS: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28640458/long-term-graft-survival-in-patients-with-chronic-antibody-mediated-rejection-with-persistent-peritubular-capillaritis-treated-with-intravenous-immunoglobulin-and-rituximab
#2
William R Mulley, Louis L Huang, Sharmila Ramessur Chandran, Anthony Longano, Liv A R Amos, Kevan R Polkinghorne, David J Nikolic-Paterson, John Kanellis
Chronic antibody mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor specific antibody positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500mg)...
June 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28639599/comparative-analysis-of-luminex-based-donor-specific-antibody-mean-fluorescence-intensity-values-with-complement-dependent-cytotoxicity-flow-crossmatch-results-in-live-donor-renal-transplantation
#3
Ajay Kumar Baranwal, Deepali Krishan Bhat, Sanjeev Goswami, Sanjay Kumar Agarwal, Gurvinder Kaur, Jasmeet Kaur, Narinder Mehra
BACKGROUND & OBJECTIVES: Antibodies specific to donor human leucocyte antigen (HLA) play a critical role in graft rejection and graft loss. In recent years, techniques for their detection have evolved significantly providing an ever-increasing degree of sensitivity and specificity, from the conventional cell-based assays to the advanced solid-phase system based on the Luminex platform. Consensus is still evolving on the routine employment of all these methods, either stand alone or in combination...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28638610/looking-for-the-needle-in-the-kidney-transplantation-haystack
#4
Josep M Cruzado, Edoardo Melilli
The diagnosis of acute rejection still relies on renal allograft biopsy. In fact, histological features including C4d staining can be useful to differentiate cellular and antibody-mediated acute rejection. However, the pathogenic mechanism to define the type of rejection is usually assessed by anti-HLA donor specific antibodies (DSA) monitoring. Suspicion of acute rejection is usually based on renal function deterioration. This method has low sensitivity. Moreover, creatinine increase follows graft injury and therefore the diagnosis is performed when there is an ongoing acute rejection...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28637884/vaccination-establishes-clonal-relatives-of-germinal-center-t-cells-in-the-blood-of-humans
#5
Antje Heit, Frank Schmitz, Sarah Gerdts, Britta Flach, Miranda S Moore, Jonathan A Perkins, Harlan S Robins, Alan Aderem, Paul Spearman, Georgia D Tomaras, Stephen C De Rosa, M Juliana McElrath
Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5(+)CD4(+) Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#6
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28634772/the-effect-of-desensitization-therapy-in-kidney-transplantation
#7
Yong Chul Kim, Mi-Yeon Yu, Jung Pyo Lee, Hajeong Lee, Sang-Il Min, Jongwon Ha, Yon Su Kim
BACKGROUND: Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear. METHODS: We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group...
June 20, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28629951/immunogenicity-of-class-i-hla-but-not-preformed-low-mfi-donor-specific-antibodies-correlates-with-outcomes-after-first-renal-transplantation
#8
A Lobashevsky, W Goggins, K Rosner, T Taber
BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-)...
June 16, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28627820/performance-of-the-liaison%C3%A2-xl-murex-rechtlv-i-ii-immunoassay-in-the-detection-of-htlv-1-2-antibodies-in-serum
#9
Pierre Gantner, Aurelie Velay, Nicolas Guigue, Heidi Barth, Marie-Josee Wendling, Constance Delaugerre, Samira Fafi-Kremer
BACKGROUND: Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) immunoassays are used for blood screen- ing from blood products, milk, and organ donors. METHODS: We assessed the performance of the DiaSorin Liaison® XL murex recHTLV-I/II immunoassay relative to the Abbott Architect® rHTLV-I/II immunoassay and with the Innogenetics immunoblot as confirmation. RESULTS: A panel of HTLV positive (n = 66) and negative (n = 30) sera was tested in both techniques within the same freeze/thaw cycle...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28627046/donor-specific-antibodies-are-associated-with-micro-and-macrovascular-coronary-disease-restrictive-myocardial-damage-and-poor-outcome-in-heart-transplanted-patients
#10
Tor Skibsted Clemmensen, Pernille Koefoed-Nielsen, Lis-Ann Jensen, Steen Hvitfeldt Poulsen, Niels Ramsing Holm, Brian Bridal Løgstrup, Evald Høj Christiansen, Jouke Dijkstra, Kamilla Pernille Bjerre Valen, Hans Eiskjaer
AIMS: We examined the relationship between donor-specific HLA antibody (DSA) presence and graft function, hemodynamics, cardiac allograft vasculopathy (CAV), and major adverse cardiac events (MACE) in stable long-term heart-transplanted (HTx) patients. METHODS: Sera from 79 patients (median 7.5 years after HTx) were analyzed for DSA presence. Graft function was evaluated by echocardiography and right heart catheterization. CAV-burden was determined by coronary angiography, optical coherence tomography (OCT), and coronary flow velocity reserve (CFVR)...
June 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28626871/a-successful-living-donor-liver-re-transplantation-for-graft-failure-within-seven-days-due-to-acute-de-novo-donor-specific-anti-hla-antibody-mediated-rejection
#11
Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Kiyotomo Abe, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Hiroshi Yagi, Naoki Shimojima, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Yasushi Fuchimoto, Kaori Kameyama, Yuko Kitagawa, Tatsuo Kuroda
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28624489/association-of-genetic-polymorphisms-of-macrophage-inhibitory-factor-mif-and-b-cell-activating-factor-baff-with-the-detection-of-donor-specific-antibodies-in-kidney-allograft-recipients
#12
Youngil Chang, Tariq Shah, David I Min
The posttransplant development of donor specific antibodies (DSA) initiates the antibody mediated rejection (AMR), which is associated with the increased rate of graft loss. One of the characteristics of AMR is the infiltration of innate immune system including macrophages, monocytes, neutrophils or NK cells. Macrophage inhibitory factor (MIF) and B-cell activating factor (BAFF) are well known cytokines that are associated with the activation of the innate immune system which can damage kidney allograft. In this article, the association of the genetic polymorphisms of MIF and BAFF with the development of DSA including Class I and II in kidney transplant patients is investigated...
June 14, 2017: Human Immunology
https://www.readbyqxmd.com/read/28621685/active-evolution-of-memory-b-cells-specific-to-viral-gh-gl-pul128-130-131-pentameric-complex-in-healthy-subjects-with-silent-human-cytomegalovirus-infection
#13
Lin Xia, Aimin Tang, Weixu Meng, Daniel C Freed, Linling He, Dai Wang, Fengsheng Li, Leike Li, Wei Xiong, Xun Gui, Robbie D Schultz, Haotai Chen, Xi He, Ryan Swoyer, Sha Ha, Yaping Liu, Charles D Morris, Yu Zhou, I-Ming Wang, Qinjian Zhao, Wenxin Luo, Ningshao Xia, Amy S Espeseth, Daria J Hazuda, Richard E Rupp, Alan D Barrett, Ningyan Zhang, Jiang Zhu, Tong-Ming Fu, Zhiqiang An
Human cytomegalovirus (HCMV) can cause life-threatening infection in immunosuppressed patients, and in utero infection that may lead to birth defects. No vaccine is currently available. HCMV infection in healthy subjects is generally asymptomatic, and virus persists as latent infection for life. Host immunity is effective against reactivation and super-infection with another strain. Thus, vaccine candidates able to elicit immune responses similar to those of natural infection may confer protection. Since neutralization is essential for prophylactic vaccines, it is important to understand how antiviral antibodies are developed in natural infection...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620648/effect-of-fc-%C3%AE-receptor-polymorphism-on-rituximab-mediated-b-cell-depletion-in-abo-incompatible-adult-living-donor-liver-transplantation
#14
Hiroshi Sakai, Yuka Tanaka, Hirofumi Tazawa, Seiichi Shimizu, Sapana Verma, Masahiro Ohira, Hiroyuki Tahara, Kentaro Ide, Kohei Ishiyama, Tsuyoshi Kobayashi, Takashi Onoe, Hideki Ohdan
BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS: SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#15
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28617221/identification-of-cancer-specific-motifs-in-mimotope-profiles-of-serum-antibody-repertoire
#16
Ekaterina Gerasimov, Alex Zelikovsky, Ion Măndoiu, Yurij Ionov
BACKGROUND: For fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient's own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4-7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients' and healthy donors' global peptide profiles of antibody specificities...
June 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28613392/donor-recipient-matching-based-on-predicted-recognizable-hla-epitopes-predicts-the-incidence-of-de-novo-donor-specific-hla-antibodies-following-renal-transplantation
#17
Nils Lachmann, Matthias Niemann, Petra Reinke, Klemens Budde, Danilo Schmidt, Fabian Halleck, Axel Pruß, Constanze Schönemann, Eric Spierings, Oliver Staeck
De novo donor-specific HLA antibodies (dnDSA) are recognized as risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2,787 consecutive kidney transplants performed 1995-2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay...
June 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28609715/an-ultrasensitive-photoelectrochemical-immunosensor-for-insulin-detection-based-on-biobr-ag2s-composite-by-in-situ-growth-method-with-high-visible-light-activity
#18
Dawei Fan, Haoyuan Wang, Malik Saddam Khan, Chunzhu Bao, Huan Wang, Dan Wu, Qin Wei, Bin Du
A novel ultrasensitive label-free immunosensor based on BiOBr/Ag2S composite with high visible-light photoelectrochemical activity was prepared for the detection of insulin. After BiOBr was modified by thioglycolic acid, Ag2S nanoparticles were grown in-situ on the surface of BiOBr hierarchical microspheres to first form novel BiOBr/Ag2S composite. When ascorbic acid (AA) was used as an efficient electron donor for scavenging photo-generated holes, BiOBr/Ag2S composite material showed excellent photoelectrochemical activity...
June 10, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28597489/development-of-a-web-based-application-and-multicountry-analysis-framework-for-assessing-interdicted-infections-and-cost-utility-of-screening-donated-blood-for-hiv-hcv-and-hbv
#19
B Custer, M P Janssen, G Hubben, M Vermeulen, M van Hulst
BACKGROUND AND OBJECTIVES: Most countries test donations for HIV, HCV and HBV using serology with or without nucleic acid testing (NAT). Cost-utility analyses provide information on the relative value of different screening options. The aim of this project was to develop an open access risk assessment and cost-utility analysis web-tool for assessing HIV, HCV and HBV screening options (http://www.isbtweb.org/working-parties/transfusion-transmitted-infectious-diseases/). An analysis for six countries (Brazil, Ghana, the Netherlands, South Africa, Thailand and USA) was conducted...
June 8, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28594749/cmv-specific-t-cell-monitoring-offers-superior-risk-stratification-of-cmv-seronegative-kidney-transplant-recipients-of-a-cmv-seropositive-donor
#20
Thomas Schachtner, Maik Stein, Petra Reinke
BACKGROUND: Detectable CMV-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV-sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV-replication. METHODS: 326 KTRs were studied and classified with respect to CMV-serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation...
June 7, 2017: Transplantation
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