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anti hla antibodies

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https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#1
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
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
#2
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
#3
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
#4
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
#5
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
#6
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/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#7
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
#8
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
https://www.readbyqxmd.com/read/29118759/b-cells-are-indispensable-for-a-novel-mouse-model-of-primary-sj%C3%A3-gren-s-syndrome
#9
Junfeng Zheng, Qiaoniang Huang, Renliang Huang, Fengyuan Deng, Xiaoyang Yue, Junping Yin, Wenjie Zhao, Yan Chen, Lifang Wen, Jun Zhou, Renda Huang, Gabriela Riemekasten, Zuguo Liu, Frank Petersen, Xinhua Yu
Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29106035/genetic-association-of-hla-drb1-multiple-polymorphisms-with-dermatomyositis-in-chinese-population
#10
Lin Jinming, Zhang Yongbiao, Qinglin Peng, Hanbo Yang, Jingli Shi, Mingliang Gu, Wenming Zhao, Guochun Wang
Genetic variation in human leukocyte antigen (HLA) plays an important role in the pathogenesis of dermatomyositis (DM). The aim of this study was to investigate the association of HLA class II with DM in China. 224 DM patients and 300 healthy controls were randomly enrolled at China-Japan Friendship Hospital. High resolution typing of HLA-DRB1 alleles was performed by sequencing based typing (SBT). The HLA-DQA1 and HLA-DQB1 alleles were determined by PCR sequence-specific primers (SSP). The frequencies of HLA-DRB1*09:01 (28...
November 6, 2017: HLA
https://www.readbyqxmd.com/read/29105756/kir-downregulation-by-il-12-15-18-unleashes-human-nk-cells-from-kir-hla-i-inhibition-and-enhances-killing-of-tumor-cells
#11
Eva-Maria Ewen, Jens H W Pahl, Matthias Miller, Carsten Watzl, Adelheid Cerwenka
To exploit autologous NK cells for cancer immunotherapy, it is highly relevant to circumvent killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition of human NK cells by HLA-I-expressing tumor cells. Here, we show that stimulation of NK cells with IL-12/15/18 for two days leads to downregulation of surface expression of the inhibitory KIR2DL2/L3, KIR2DL1 and KIR3DL1 receptors on peripheral blood NK cells. Downregulation of KIR expression was attributed to decreased KIR mRNA levels which could be re-induced already 3 days after re-culture in IL-2...
November 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29101003/fatal-accelerated-rejection-with-a-prominent-natural-killer-cell-infiltrate-in-a-heart-transplant-recipient-with-peripartum-cardiomyopathy
#12
Ali Javaheri, Amber R Wang, Eline Luning Prak, Priti Lal, Lee R Goldberg, Malek Kamoun
Accelerated rejection is uncommon after cardiac transplantation. The mechanism is hypothesized to be mediated by cytotoxic T cells and anti-HLA antibodies resulting from a memory response to the donor allograft in sensitized patients. A role for Natural Killer (NK) cell in cellular rejection has also been suggested. We report a case of fulminant accelerated rejection in a heart transplant recipient, with a history of peripartum cardiomyopathy (PPMC). The patient had no pre-transplant donor specific antibody and flow cytometric T and B cell crossmatches were negative...
October 31, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/29100943/the-avidity-of-cross-reactive-virus-specific-t-cells-for-their-viral-and-allogeneic-epitopes-is-variable-and-depends-on-epitope-expression
#13
Heleen van den Heuvel, Kirstin M Heutinck, Ellen M W van der Meer-Prins, Marry E I Franke-van Dijk, Paula P M C van Miert, Xiaoqian Zhang, Ineke J M Ten Berge, Frans H J Claas
Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through cross-reactivity of their T-cell receptor (TCR). In a transplantation setting, such allo-HLA cross-reactivity may contribute to harmful immune responses towards the allograft, provided that the cross-reactive T cells get sufficiently activated upon recognition of the allo-HLA. An important determinant of T-cell activation is TCR avidity, which to date, has remained largely unexplored for allo-HLA-cross-reactive virus-specific T cells. For this purpose, cold target inhibition assays were performed using allo-HLA-cross-reactive virus-specific memory CD8(+) T-cell clones as responders, and syngeneic cells loaded with viral peptide and allogeneic cells as hot (radioactively-labeled) and cold (non-radioactively-labeled) targets...
October 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/29090853/preexisting-anti-hla-donor-specific-antibodies-in-pediatric-renal-transplant-recipients-a-new-challenge
#14
EDITORIAL
Lutz T Weber
No abstract text is available yet for this article.
November 1, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29089045/a-young-female-presenting-with-unilateral-sacroiliitis-following-dengue-virus-infection-a-case-report
#15
W D Jayamali, H M M T B Herath, Aruna Kulatunga
BACKGROUND: Dengue is a common arthropod-borne viral infection in Sri Lanka which is spread by the mosquitos of the genus Aedes. The clinical features of dengue include high-grade fever associated with arthralgia and myalgia. However, dengue virus is not considered an arthritogenic virus. We report a case of a previously healthy young female who presented with imaging-confirmed right-sided sacroiliitis 10 days after developing dengue fever. This is the first reported case that shows a possible link between dengue infection and development of arthritis...
November 1, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29083383/evaluation-of-multiple-diagnostic-indicators-in-comparison-to-the-intestinal-biopsy-as-the-golden-standard-in-diagnosing-celiac-disease-in-children
#16
Elisabet Hollén, Malin Farnebäck, Tony Forslund, Karl-Eric Magnusson, Tommy Sundqvist, Karin Fälth-Magnusson
Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the disease. The criteria for diagnosing CD were previously based primarily on histologic evaluation of small intestinal biopsies, but nowadays are often based only on blood tests and symptoms. In this context, we elucidated the accuracy of three diagnostic indicators for CD, alone or in combination...
November 25, 2016: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29075627/characteristics-of-donor-specific-antibodies-associated-with-antibody-mediated-rejection-in-lung-transplantation
#17
Antoine Roux, Ines Bendib Le Lan, Sonia Holifanjaniaina, Kimberly A Thomas, Clément Picard, Dominique Grenet, Sandra De Miranda, Benoit Douvry, Laurence Beaumont-Azuar, Edouard Sage, Jérôme Devaquet, Elise Cuquemelle, Morgan Le Guen, Caroline Suberbielle, Chantal Gautreau, Marc Stern, Maura Rossetti, Abdul Monem Hamid, Francois Parquin
Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010-2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMR(Pos), n = 22, and AMR(Neg), n = 83, respectively) were compared...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29070994/nivolumab-induced-myocarditis-concomitant-with-myasthenia-gravis
#18
Yoko Fukasawa, Kazuya Sasaki, Maika Natsume, Makoto Nakashima, Shuji Ota, Kiyotaka Watanabe, Yoshihisa Takahashi, Fukuo Kondo, Ken Kozuma, Nobuhiko Seki
We report a 69-year-old female patient with advanced lung cancer who developed myocarditis concomitant with myasthenia gravis (MG), also known as "Herzmyasthenie," after 3 cycles of nivolumab administration. Her initial symptoms were general malaise and double vision. However, her myocarditis deteriorated rapidly the following day, necessitating a temporary pacemaker and noninvasive positive pressure ventilation in the intensive care unit. Immunohistochemical examination of a myocardial biopsy suggested an immune response on the basis of HLA associations...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29070529/anticitrullinated-protein-peptide-antibody-multiplexing-defines-an-extended-group-of-acpa-positive-rheumatoid-arthritis-patients-with-distinct-genetic-and-environmental-determinants
#19
Johan Rönnelid, Monika Hansson, Linda Mathsson-Alm, Martin Cornillet, Evan Reed, Per-Johan Jakobsson, Lars Alfredsson, Rikard Holmdahl, Karl Skriner, Guy Serre, Karin Lundberg, Lars Klareskog
INTRODUCTION: The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we have investigated the fine specificity of individual ACPA responses and the biological impact of additional ACPA reactivity among anti-CCP2-negative patients...
October 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29066027/interferon-beta-specific-t-cells-are-associated-with-the-development-of-neutralizing-antibodies-in-interferon-beta-treated-multiple-sclerosis-patients
#20
Sudhakar Reddy Kalluri, Verena Grummel, Zsuzsanna Hracsko, Viola Pongratz, Verena Pernpeintner, Christiane Gasperi, Dorothea Buck, Bernhard Hemmer
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β...
October 20, 2017: Journal of Autoimmunity
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