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https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#1
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28631096/a-case-of-nivolumab-related-cholangitis-and-literature-review-how-to-look-for-the-right-tools-for-a-correct-diagnosis-of-this-rare-immune-related-adverse-event
#2
Francesco Gelsomino, Giovanni Vitale, Andrea Ardizzoni
Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28629173/autophagic-mechanism-in-anti-cancer-immunity-its-pros-and-cons-for-cancer-therapy
#3
REVIEW
Ying-Ying Li, Lynn G Feun, Angkana Thongkum, Chiao-Hui Tu, Shu-Mei Chen, Medhi Wangpaichitr, Chunjing Wu, Macus T Kuo, Niramol Savaraj
Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28624334/seasonality-and-autoimmune-diseases-the-contribution-of-the-four-seasons-to-the-mosaic-of-autoimmunity
#4
REVIEW
Abdulla Watad, Shir Azrielant, Nicola Luigi Bragazzi, Kassem Sharif, Paula David, Itay Katz, Gali Aljadeff, Mariana Quaresma, Galya Tanay, Mohammad Adawi, Howard Amital, Yehuda Shoenfeld
Autoimmune diseases (ADs) are a heterogeneous groups of diseases that occur as a results of loss of tolerance to self antigens. While the etiopathogeneis remain obscure, different environmental factors were suggested to have a role in the development of autoimmunity, including infections, low vitamin D levels, UV radiation, and melatonin. Interestingly, such factors possess seasonal variation patterns that could influence disease development, severity and progression. Vitamin D levels which reach a nadir during late winter and early spring is correlated with increased disease activity, clinical severity as well as relapse rates in several disease entities including multiple sclerosis (MS), non-cutaneous flares of systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis (RA)...
June 14, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28623084/pathogenesis-of-human-systemic-lupus-erythematosus-a-cellular-perspective
#5
REVIEW
Vaishali R Moulton, Abel Suarez-Fueyo, Esra Meidan, Hao Li, Masayuki Mizui, George C Tsokos
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors...
June 13, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28621731/the-therapeutic-benefit-of-bacterial-membrane-vesicles
#6
REVIEW
Natalie J Bitto, Maria Kaparakis-Liaskos
The therapeutic potential of extracellular vesicles from eukaryotes has gained strong interest in recent years. However, research into the therapeutic application of their bacterial counterparts, known as bacterial membrane vesicles, is only just beginning to be appreciated. Membrane vesicles (MVs) from both Gram-positive and Gram-negative bacteria offer significant advantages in therapeutic development, including large-scale, cost effective production and ease of molecular manipulation to display foreign antigens...
June 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28615655/secreted-igm-deficiency-leads-to-increased-bcr-signaling-that-results-in-abnormal-splenic-b-cell-development
#7
Dimitrios Tsiantoulas, Mate Kiss, Barbara Bartolini-Gritti, Andreas Bergthaler, Ziad Mallat, Hassan Jumaa, Christoph J Binder
Mice lacking secreted IgM (sIgM (-/-)) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells in sIgM (-/-) mice display increased B cell receptor (BCR) signaling as judged by increased levels of phosphorylated Bruton's tyrosine kinase (pBtk), phosphorylated Spleen tyrosine kinase (pSyk), and nuclear receptor Nur77. Low dosage treatment with the pBtk inhibitor Ibrutinib reversed the altered B cell development in the spleen of sIgM (-/-) mice, suggesting that sIgM regulate splenic B cell differentiation by decreasing BCR signaling...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602290/a-sensitive-and-disposable-electrochemical-immunosensor-for-detection-of-sox2-a-biomarker-of-cancer
#8
Elif Burcu Aydın, Mustafa Kemal Sezgintürk
A novel, sensitive, disposable indium tin oxide (ITO)-based electrochemical immunosensor was developed firstly for simple, rapid determination of Sex-determining region Y-box 2 (SOX2). SOX2 is a cancer biomarker and used for detecting small cell lung cancer, lung adenocarcinoma, squamous cell carcinoma, skin cancer, prostate cancer, and breast cancer. In this study, a disposable ITO thin film based electrode was used as working electrode for biosensing the interaction between SOX2 antigen and anti-SOX2 antibody...
September 1, 2017: Talanta
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#9
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28597552/branched-chain-%C3%AE-ketoacid-dehydrogenase-kinase-111-130-a-t-cell-epitope-that-induces-both-autoimmune-myocarditis-and-hepatitis-in-a-j-mice
#10
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A Uzal, Jennifer L Strande, Gustavo A Delhon, Jean-Jack Riethoven, David Steffen, Jay Reddy
INTRODUCTION: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread. METHODS: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKDk ) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver...
June 9, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28589115/regulatory-t-cells-in-allergy-and-asthma
#11
REVIEW
Elena Martín-Orozco, María Norte-Muñoz, Javier Martínez-García
The immune system's correct functioning requires a sophisticated balance between responses to continuous microbial challenges and tolerance to harmless antigens, such as self-antigens, food antigens, commensal microbes, allergens, etc. When this equilibrium is altered, it can lead to inflammatory pathologies, tumor growth, autoimmune disorders, and allergy/asthma. The objective of this review is to show the existing data on the importance of regulatory T cells (Tregs) on this balance and to underline how intrauterine and postnatal environmental exposures influence the maturation of the immune system in humans...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28587995/duffy-blood-group-system-new-genotyping-method-and-distribution-in-a-brazilian-extra-amazonian-population
#12
Marina Lobato Martins, Adão Rogerio da Silva, Hadassa Campos Santos, Michelle Teodoro Alves, Luciana Cayres Schmidt, Stela Brener Vertchenko, Luci Maria SantAna Dusse, Maria Clara Fernandes da Silva Malta
Duffy blood group system is of interest in several fields of science including transfusion medicine, immunology and malariology. Although some methods have been developed for Duffy polymorphism genotyping, not all of them have been sufficiently described and validated, and all present limitations. At the same time, the frequency of Duffy alleles and antigens in some densely populated regions of the world are still missing. In this study we present new tests for genotyping the major alleles of the Duffy blood system and describe Duffy alleles and antigens in blood donors and transfusion-dependent patients in Minas Gerais, Brazil...
June 3, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28587625/anti-nuclear-autoantibodies-in-the-general-german-population-prevalence-and-lack-of-association-with-selected-cardiovascular-and-metabolic-disorders-findings-of-a-multicenter-population-based-study
#13
Manas K Akmatov, Nadja Röber, Wolfgang Ahrens, Dieter Flesch-Janys, Julia Fricke, Halina Greiser, Kathrin Günther, Rudolf Kaaks, Yvonne Kemmling, Bastian Krone, Jakob Linseisen, Christa Meisinger, Susanne Moebus, Nadia Obi, Carlos A Guzman, Karsten Conrad, Frank Pessler
BACKGROUND: We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. METHODS: We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples...
June 6, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28587470/surface-engineering-of-poly-methylmethacrylate-effects-on-fluorescence-immunoassay
#14
Peter W Akers, Nam Cao Hoai Le, Andrew R J Nelson, Milena McKenna, Christy O'Mahony, Duncan J McGillivray, Vladimir Gubala, David E Williams
The authors present surface engineering modifications through chemistry of poly(methylmethacrylate) (PMMA) that have dramatic effects on the result of surface-bound fluorescence immunoassays, both for specific and nonspecific signals. The authors deduce the most important effect to be clustering of antibodies on the surface leading to significant self-quenching. Secondary effects are attributable to the formation of sparse multilayers of antibody. The authors compare PMMA as an antibody support surface with ultraviolet-ozone oxidized PMMA and also to substrates that were, after the oxidation, surface modified by a four-unit poly(ethyleneglycol) carboxylic acid (PEG4), a branched tricarboxylic acid, and a series of carboxylic acid-terminated dendrimers, from generation 1...
June 6, 2017: Biointerphases
https://www.readbyqxmd.com/read/28578649/peptides-against-autoimmune-neurodegeneration
#15
Alexey Stepanov, Yakov Lomakin, Alexander Gabibov, Alexey Belogurov
The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body...
June 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28577615/maternal-allo-recognition-of-the-fetus
#16
REVIEW
Ashley Moffett, Olympe Chazara, Francesco Colucci
Immunological adjustments are needed to accommodate the close contact between two genetically different individuals, the mother and her baby, during mammalian pregnancy. Contact occurs between fetal somatic or placental cells that enter the maternal systemic circulation or between uterine immune cells and the invading extravillous trophoblast. Here we discuss two main types of maternal allo-recognition of the fetus. One depends on avoidance of maternal T cells recognizing and responding to paternally-derived non-self human leukocyte antigens class I and class I allotypes...
June 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28576753/the-function-of-regulatory-t-cells-at-the-ocular-surface-review
#17
REVIEW
William Foulsham, Anna Marmalidou, Afsaneh Amouzegar, Giulia Coco, Yihe Chen, Reza Dana
Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface...
May 30, 2017: Ocular Surface
https://www.readbyqxmd.com/read/28573279/an-automated-and-portable-microfluidic-chemiluminescence-immunoassay-for-quantitative-detection-of-biomarkers
#18
Binfeng Hu, Juanjuan Li, Lei Mou, Yong Liu, Jinqi Deng, Wei Qian, Jiashu Sun, Ruitao Cha, Xingyu Jiang
Microfluidic platforms capable of automated, rapid, sensitive, and quantitative detection of biomarkers from patient samples could make a major impact on clinical or point-of-care (POC) diagnosis. In this work, we realize an automated diagnostic platform composed of two main components: (1) a disposable, self-contained, and integrated microfluidic chip and (2) a portable instrument that carries out completely automated operations. To demonstrate its potential for real-world application, we use injection molding for mass fabrication of the main components of disposable microfluidic chips...
June 2, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28572802/chimeric-antigen-receptor-engineered-nk-92-cells-an-off-the-shelf-cellular-therapeutic-for-targeted-elimination-of-cancer-cells-and-induction-of-protective-antitumor-immunity
#19
Congcong Zhang, Pranav Oberoi, Sarah Oelsner, Anja Waldmann, Aline Lindner, Torsten Tonn, Winfried S Wels
Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28572052/hematopoietic-stem-cell-transplantation-in-autoimmune-disorders-from-immune-regulatory-processes-to-clinical-implications
#20
REVIEW
Margit Zeher, Gábor Papp, Britt Nakken, Peter Szodoray
Autoimmune diseases are characterized by the development of autoreactive T- and B-cells targeting self-antigens, which eventually can result in chronic and persistent organ damage. The autologous hematopoietic stem cell transplantation (AHSCT) opened new avenues in the treatment of patients with severe, treatment-resistant autoimmune diseases. This paper reviews the immune-regulatory mechanisms behind AHSCT, and also summarizes the experiences of clinical practice related to the therapy in organ-specific and systemic autoimmune diseases...
May 29, 2017: Autoimmunity Reviews
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