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https://www.readbyqxmd.com/read/29159992/clinical-and-histopathologic-features-of-antibody-mediated-rejection-among-pediatric-renal-transplant-recipients-with-preformed-vs-de-novo-donor-specific-antibodies
#1
Justin A Steggerda, Irene K Kim, Mark Haas, Xiaohai Zhang, Alexis Kang, Helen Pizzo, Elaine Kamil, Stanley Jordan, Dechu Puliyanda
Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy-proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow-up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA...
December 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29159718/genetics-and-epigenetics-in-the-pathogenesis-of-primary-biliary-cholangitis
#2
REVIEW
Satoru Joshita, Takeji Umemura, Eiji Tanaka, Masao Ota
Primary biliary cholangitis (PBC) is a chronic, slowly progressive cholestatic autoimmune liver disease predominantly afflicting women. PBC is characterized by the presence of disease-specific antimitochondrial antibodies and the histological destruction of intrahepatic bile ducts, which eventually lead to cirrhosis and hepatic failure. Fortunately, ursodeoxycholic acid therapy has improved the outcome of the vast majority of PBC cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades...
November 20, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/29157993/pronase-independent-flow-cytometry-crossmatching-of-rituximab-treated-patients
#3
Mats Alheim, Lars Wennberg, Ann-Charlotte Wikström
ABO-incompatible (ABOi) kidney transplantation has become an established strategy to increase the number of available living donors. At our center, the conditioning protocol for ABOi patients is based on anti-A/B antibody removal and depletion of B cells with the anti-CD20 mAb rituximab (Mabthera®). It is known that even low amounts of remaining rituximab in serum of patients results in false positive B cell cross match results, masking detection of potentially harmful donor human leukocyte antigen (HLA) specific antibodies...
November 17, 2017: Human Immunology
https://www.readbyqxmd.com/read/29157597/donor-specific-hla-antibodies-in-predicting-crossmatch-outcome-comparison-of-three-different-laboratory-techniques
#4
J P Peräsaari, T Jaatinen, J Merenmies
The virtual crossmatch, which is based on single antigen bead technology, is used in the prediction of crossmatch results. However, this assay differs in sensitivity and specificity from crossmatch methods. In our study, the results of physical crossmatches, performed with three different methods, were assessed against virtual crossmatch results. The aim was to determine the potential cut-off values for donor specific antibodies (DSA) that would predict the crossmatch results obtained by different methods. The results of different crossmatch techniques were correlated with the virtual crossmatch...
November 17, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/29154771/in-vitro-blockade-of-the-cd4-receptor-co-signal-in-antigen-specific-t-cell-stimulation-cultures-induces-the-outgrowth-of-potent-cd4-independent-t-cell-effectors
#5
Sarah Vatter, Maximilian Schmid, Claudia Gebhard, Carina Mirbeth, Sebastian Klobuch, Michael Rehli, Wolfgang Herr, Simone Thomas
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus. Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach...
November 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29150964/de-novo-donor-specific-hla-antibodies-after-combined-intestinal-and-vascularised-composite-allotransplantation
#6
Annemarie Weissenbacher, Georgios Vrakas, Mian Chen, Srikanth Reddy, Philip Allan, Henk Giele, Martin Cnm Barnardo, Anil Vaidya, Peter J Friend, Susan V Fuggle
Combining vascularised composite allotransplantation (VCA) with intestinal transplantation to achieve primary abdominal closure has become a feasible procedure. Besides facilitating closure, the abdominal wall can be used to monitor intestinal rejection. As the inclusion of a VCA raises the possibility of an enhanced alloimmune response, we investigated the incidence and clinical effect of de novo donor specific HLA antibodies (dnDSA) in a cohort of patients receiving an intestinal transplant with or without a VCA...
November 18, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29150812/factors-influencing-platelet-transfusion-refractoriness-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#7
Pilar Solves, Jaime Sanz, Carmen Freiria, Marta Santiago, Ana Villalba, Inés Gómez, Pau Montesinos, Juan Montoro, Jose Luis Piñana, José Ignacio Lorenzo, Nieves Puig, Guillermo F Sanz, Miguel Ángel Sanz, Nelly Carpio
Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation...
November 17, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29149956/comparison-between-total-igg-c1q-and-c3d-single-antigen-bead-assays-in-detecting-class-i-complement-binding-anti-hla-antibodies
#8
M A Moreno Gonzales, D G Mitema, B H Smith, C A Schinstock, M D Stegall, L L Wakefield, N A Henderson, S R DeGoey, J D Kreuter, M J Gandhi
BACKGROUND: Complement-binding donor-specific antibodies (DSAs) are associated with antibody-mediated rejection and allograft loss. Novel single antigen bead (SAB) assays-that is, complement component 1q (C1q) and complement component 3d (C3d) assays-have been developed to specifically detect complement-binding DSA, but it remains unclear whether these assays have an improved ability to detect complement-binding DSA as compared with using the total IgG SAB assay with a high mean fluorescence intensity (MFI) cutoff...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29146602/donor-specific-and-nonspecific-hla-antibodies-and-outcome-post-lung-transplantation
#9
Stijn E Verleden, Bart M Vanaudenaerde, Marie-Paul Emonds, Dirk E Van Raemdonck, Arne P Neyrinck, Geert M Verleden, Robin Vos
Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are associated with chronic lung allograft dysfunction (CLAD) and mortality post lung transplantation, but data concerning prevalence, time of onset, persistence and effects on long-term outcome remain scarce.We assessed the association between HLA antibodies and CLAD-free and graft survival in a cohort of 362 patients. We stratified our analysis according to DSA status, persistence of antibodies and timing of antibodies (pre-transplant, early or late post-transplant)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29145880/anti-nf155-chronic-inflammatory-demyelinating-polyradiculoneuropathy-strongly-associates-to-hla-drb15
#10
Laura Martinez-Martinez, Ma Cinta Lleixà, Gemma Boera-Carnicero, Andrea Cortese, Jérôme Devaux, Ana Siles, Yusuf Rajabally, Alicia Martinez-Piñeiro, Alejandra Carvajal, Julio Pardo, Emilien Delmont, Shahram Attarian, Jordi Diaz-Manera, Ilaria Callegari, Enrico Marchioni, Diego Franciotta, Luana Benedetti, Guiseppe Lauria, Oscar de la Calle Martin, Cándido Juárez, Isabel Illa, Luis Querol
BACKGROUND: The aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies. METHODS: Thirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele...
November 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29144053/the-impact-of-flow-pra-on-outcome-in-pediatric-heart-recipients-in-modern-era-an-analysis-of-the-pediatric-heart-transplant-study-database
#11
B B Das, E Pruitt, K Molina, W Ravekes, S Auerbach, A Savage, L Knox, J K Kirklin, D C Naftel, D Hsu
Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA > 20%. Patients with a PRA > 20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%...
November 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#12
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29140548/a-phase-ib-open-label-single-arm-study-to-assess-the-safety-pharmacokinetics-and-impact-on-humoral-sensitization-of-sanguinate-infusion-in-patients-with-end-stage-renal-disease
#13
Bassam G Abu Jawdeh, E Steve Woodle, Abbie D Leino, Paul Brailey, Simon Tremblay, Tonya Dorst, Mouhamad H Abdallah, Amit Govil, Daniel Byczkowski, Hemant Misra, Abraham Abuchowski, Rita R Alloway
The endeavor to study desensitization in kidney transplantation hasn't been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive 3 weekly infusions of SG (320mg/Kg)...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29138371/-adaptation-of-anti-pd-1-anti-pd-l1-antibody-from-the-viewpoint-of-analysis-of-tumor-microenvironment
#14
Kousaku Mimura, Yuko Nakayama, Tadao Nakazawa, Koji Kono
The response rate of anti-PD-1/anti-PD-L1antibody alone is about 20 to 30%and the development of biomarker for them is important to know their indication. Based on previous reports and our research results, we suggested that basic candidates of biomarker for anti-PD-1/anti-PD-L1antibody are the expression of PD-L1and HLA class I on cancer cells and the invasion of CD8 positive T cells in tumor microenvironment. Furthermore, in addition to these conditions, regulatory T cells and immune cells expressing PD-L1in tumor microenvironment, and microsatellite instability of cancer cells will be considered in the future...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#15
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29135340/generation-and-testing-anti-influenza-human-monoclonal-antibodies-in-a-new-humanized-mouse-model-draga-hla-a2-hla-dr4-rag1-ko-il-2r%C3%AE-c-ko-nod
#16
Mirian Mendoza, Angela Ballesteros, Qiu Qi, Luis Pow Sang, Soumya Shashikumar, Sofia Casares, Teodor-D Brumeanu
Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rγc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb)...
November 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#17
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29128670/synchronous-immune-alterations-mirror-clinical-response-during-allergen-immunotherapy
#18
Amedee Renand, Mohamed H Shamji, Kristina M Harris, Tielin Qin, Erik Wambre, Guy W Scadding, Peter A Wurtzen, Stephen J Till, Alkis Togias, Gerald T Nepom, William W Kwok, Stephen R Durham
BACKGROUND: Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS(∗) trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. OBJECTIVE: To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation...
November 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#19
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29119564/intracranial-hemorrhages-in-neonates-born-from-32-weeks-of-gestation-low-frequency-of-associated-fetal-and-neonatal-alloimmune-thrombocytopenia-a-register-based-study
#20
Erle Refsum, Stellan Håkansson, Anette Mörtberg, Agneta Wikman, Magnus Westgren
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH...
November 8, 2017: Transfusion
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