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Clinical & Translational Immunology

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https://www.readbyqxmd.com/read/28090323/high-thioredoxin-1-levels-in-rheumatoid-arthritis-patients-diminish-binding-and-signalling-of-the-monoclonal-antibody-tregalizumab
#1
Katharina Heim, Benjamin Dälken, Stefanie Faust, Faiza Rharbaoui, Andre Engling, Holger Wallmeier, Theodor Dingermann, Heinfried H Radeke, Jörg Schüttrumpf, Marcus Gutscher
The humanized non-depleting anti-CD4 monoclonal antibody Tregalizumab (BT-061) is able to selectively activate the suppressive function of regulatory T cells and has been investigated up to phase IIb in clinical trials in patients suffering from rheumatoid arthritis (RA). A pharmacokinetic-pharmacodynamic model based on clinical data from RA and healthy volunteers, which used the cell surface CD4 downmodulation as marker of activity, confirmed a stronger effect in healthy volunteers compared with RA patients...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090322/vaccination-to-gain-humoral-immune-memory
#2
REVIEW
Jana Sarkander, Shintaro Hojyo, Koji Tokoyoda
The concept of immune memory forms the biological basis for vaccination programs. Despite advancements in the field of immune memory and vaccination, most current vaccines are evaluated by magnitude of antigen-specific antibody titers in serum or mucosa after vaccination. It has been shown, however, that antibody-mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, suggesting that assessment of vaccine efficacy should be performed for several years after vaccination...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#3
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090320/immunopathogenesis-of-granulomas-in-chronic-autoinflammatory-diseases
#4
REVIEW
Wilhelmina Maria Cornelia Timmermans, Jan Alexander Michael van Laar, Petrus Martinus van Hagen, Menno Cornelis van Zelm
Granulomas are clusters of immune cells. These structures can be formed in reaction to infection and display signs of necrosis, such as in tuberculosis. Alternatively, in several immune disorders, such as sarcoidosis, Crohn's disease and common variable immunodeficiency, non-caseating granulomas are formed without an obvious infectious trigger. Despite advances in our understanding of the human immune system, the pathogenesis underlying these non-caseating granulomas in chronic inflammatory diseases is still poorly understood...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090319/the-role-of-liver-sinusoidal-cells-in-local-hepatic-immune-surveillance
#5
REVIEW
Dirk Wohlleber, Percy A Knolle
Although the liver's function as unique immune organ regulating immunity has received a lot of attention over the last years, the mechanisms determining hepatic immune surveillance against infected hepatocytes remain less well defined. Liver sinusoidal cells, in particular, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), serve as physical platform for recruitment and anchoring of blood-borne immune cells in the liver. Liver sinusoidal cells also function as portal of entry for infectious microorganisms targeting the liver such as hepatotropic viruses, bacteria or parasites...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090318/dengue-virus-antibodies-enhance-zika-virus-infection
#6
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Scott F Michael, Sharon Isern
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090317/all-trans-retinoic-acid-enhances-cytotoxic-effect-of-t-cells-with-an-anti-cd38-chimeric-antigen-receptor-in-acute-myeloid-leukemia
#7
Tetsumi Yoshida, Keichiro Mihara, Yoshifumi Takei, Kazuyoshi Yanagihara, Takanori Kubo, Joyeeta Bhattacharyya, Chihaya Imai, Tatsuji Mino, Yoshihiro Takihara, Tatsuo Ichinohe
We reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia (AML) blasts not expressing CD38, it is necessary to induce or increase the intensity of CD38 expression. A lactate dehydrogenase (LDH)-releasing assay and flow cytometry showed that anti-CD38-CAR T cells were cytotoxic against AML lines (THP-1 and CMK) expressing high CD38 levels (>99%), in time- and number of effector-dependent manners...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090316/the-role-of-tumour-necrosis-factor-in-hepatitis-b-infection-jekyll-and-hyde
#8
REVIEW
Zina Valaydon, Marc Pellegrini, Alexander Thompson, Paul Desmond, Peter Revill, Gregor Ebert
Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090315/chronic-mucocutaneous-candidiasis-disease-associated-with-inborn-errors-of-il-17-immunity
#9
REVIEW
Satoshi Okada, Anne Puel, Jean-Laurent Casanova, Masao Kobayashi
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990288/infiltrating-monocytes-in-liver-injury-and-repair
#10
REVIEW
Katherine J Brempelis, Ian N Crispe
Noninfectious liver injury causes many acute and chronic liver diseases around the globe, and particularly in developed nations. Bone marrow-derived monocytes infiltrate the damaged liver tissue and are a critical component of the innate immune response that may drive injury resolution or host death in the short term or chronic inflammation, fibrosis and hepatocellular carcinoma in the long term. Monocytes often play dual roles in liver injury-both perpetuating inflammation and promoting resolution of inflammation and fibrosis...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990287/coeliac-disease-a-unique-model-for-investigating-broken-tolerance-in-autoimmunity
#11
REVIEW
Melinda Y Hardy, Jason A Tye-Din
Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II association and the presence of pathogenic CD4(+) T cells and autoantibodies. CD8(+) intraepithelial lymphocytes specifically target and destroy intestinal epithelium in response to stress signals and not a specific antigen...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990286/guanylate-binding-protein-5-is-a-marker-of-interferon-%C3%AE-induced-classically-activated-macrophages
#12
Yukio Fujiwara, Yoshiyuki Hizukuri, Kyoko Yamashiro, Naoyuki Makita, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara, Yasuhiro Hayashi
Macrophage activation is the main immunological process occurring during the development of several diseases, and the heterogeneity of macrophage activation or differentiation has been suggested to be involved in disease progression. In the present study, we attempted to identify molecules specifically expressed on human classically activated macrophages (M1) to investigate the significance of the M1-like phenotype in human diseases. Human monocyte-derived macrophages were differentiated into M1, M2a, M2b and M2c phenotypes, and also M1(-) (the M1 phenotype differentiated with interferon-γ) to eliminate the strong effects of lipopolysaccharides (LPS) on the gene expression profile...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990285/non-small-cell-lung-cancer-is-characterised-by-a-distinct-inflammatory-signature-in-serum-compared-with-chronic-obstructive-pulmonary-disease
#13
Hanne Astrid Eide, Ann Rita Halvorsen, Vandana Sandhu, Anne Fåne, Janna Berg, Vilde Drageset Haakensen, Elin H Kure, Odd Terje Brustugun, Cecilie Essholt Kiserud, Jon Amund Kyte, Åslaug Helland
Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990284/a-structure-function-approach-to-optimizing-tlr4-ligands-for-human-vaccines
#14
Darrick Carter, Christopher B Fox, Tracey A Day, Jeffrey A Guderian, Hong Liang, Tom Rolf, Julie Vergara, Zachary K Sagawa, Greg Ireton, Mark T Orr, Anthony Desbien, Malcolm S Duthie, Rhea N Coler, Steven G Reed
Adjuvants are combined with vaccine antigens to enhance and modify immune responses, and have historically been primarily crude, undefined entities. Introducing toll-like receptor (TLR) ligands has led to a new generation of adjuvants, with TLR4 ligands being the most extensively used in human vaccines. The TLR4 crystal structures demonstrate extensive contact with their ligands and provide clues as to how they discriminate a broad array of molecules and activate or attenuate innate, as well as adaptive, responses resulting from these interactions...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990283/the-gut-microbiota-and-immune-regulation-the-fate-of-health-and-disease
#15
EDITORIAL
Eliana Mariño
No abstract text is available yet for this article.
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27867517/protective-immunity-to-liver-stage-malaria
#16
REVIEW
Lauren E Holz, Daniel Fernandez-Ruiz, William R Heath
Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27867516/autoantibodies-against-cd80-in-patients-with-copd
#17
Xu Min Luo, Xin Yan Liu, Ji Hong Tang, Wei Yang, Zhen Hua Ni, Qing Ge Chen, Xiongbiao Wang
Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and possibly an autoimmune disease. The components of the autoimmune response in the circulatory system are of considerable interest to clinicians. Because aberrations of costimulation status have been noted in COPD, the presence of autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of patients. Recombinant rs1CD80 (lacking the transmembrane domain of CD80) was used for Western blot analysis and ELISA to investigate the presence of autoantibodies in sera of patients with stable COPD and in controls without COPD...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27867515/the-cd8-t-cell-response-during-tolerance-induction-in-liver-transplantation
#18
REVIEW
Yik Chun Wong, Geoffrey W McCaughan, David G Bowen, Patrick Bertolino
Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing 'operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27867514/hepatitis-c-virus-drives-the-pathogenesis-of-hepatocellular-carcinoma-from-immune-evasion-to-carcinogenesis
#19
Miriam Canavese, Danushka Wijesundara, Guy J Maddern, Branka Grubor-Bauk, Ehud Hauben
Persistent hepatitis C virus (HCV) infection is associated with high incidence of hepatocellular carcinoma (HCC), the most common primary malignancy of the liver with over half a million new cases diagnosed annually worldwide. The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and its activation by environmental chemicals and by its endogenous ligand kynurenine (Kyn) has been implicated in a variety of tumour-promoting processes such as transformation, tumorigenesis and in immunosuppression that enables tumour survival and growth...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27766148/expression-profile-of-novel-cell-surface-molecules-on-different-subsets-of-human-peripheral-blood-antigen-presenting-cells
#20
Daniela Damasceno, Martín Pérez Andrés, Wouter Bl van den Bossche, Juan Flores-Montero, Sandra de Bruin, Cristina Teodosio, Jacques Jm van Dongen, Alberto Orfao, Julia Almeida
Although major steps have been recently made in understanding the role of the distinct subsets of dendritic cells (DC)/antigen-presenting cells (APC), further studies are required to unravel their precise role, including in-depth immunophenotypic characterisation of these cells. Here, we used eight-colour flow cytometry to investigate the reactivity of a panel of 72 monoclonal antibodies (including those clustered in seven new Cluster of Differentiation, CD) on different subsets of APC in peripheral blood (PB) samples from five healthy adults...
September 2016: Clinical & Translational Immunology
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