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Immunity, Inflammation and Disease

Takayuki Jodai, Chieko Yoshida, Ryo Sato, Yosuke Kakiuchi, Nahoko Sato, Shinji Iyama, Tomoko Kimura, Koichi Saruwatari, Sho Saeki, Hidenori Ichiyasu, Kazuhiko Fujii, Yusuke Tomita
INTRODUCTION: The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death-ligand 2 (PD-L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo-responsive Th2 cells via the PD-1/PD-L2 inhibitory pathway in lung could be reawaken by PD-1 blockade therapy. METHODS: We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2-associated pulmonary disease, triggered by nivolumab, an anti-PD-1 antibody, in an advanced non-small cell lung cancer patient...
November 21, 2018: Immunity, Inflammation and Disease
Ranbir Kaulsay, Duc Tung Nguyen, Hans Christian Kuhl
INTRODUCTION: Most allergic rhinitis (AR) patients have moderate-to-severe, persistent disease. Meda Pharma's AzeFlu (MP-AzeFlu) combines intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation in a single device to treat AR. This prospective, noninterventional study sought to assess the effectiveness of MP-AzeFlu (one spray/nostril twice daily; 548 µg AZE/200 µg FP daily dose) in relieving AR symptom severity. METHODS: A visual analogue scale (VAS) was used prior to MP-AzeFlu treatment on days 0, 1, 3, 7, 14, 21, 28, 35, and 42 by 53 persistent AR (PER) patients seen in routine clinical practice in Ireland...
December 2018: Immunity, Inflammation and Disease
Ramin Lotfi, Lena Steppe, Regina Hang, Markus Rojewski, Marina Massold, Bernd Jahrsdörfer, Hubert Schrezenmeier
INTRODUCTION: MSCs are often found within tumors, promote cancer progression and enhance metastasis. MSCs can act as immuosuppressive cells, partially due to the expression of the enzyme indoleamine dioxygenase (IDO) which converts tryptophan to kynurenine. Decreased concentration of tryptophan and increased kynurenine, both interfere with effective immune response. Damage associated molecular patterns (DAMPs) including ATP are found within the tumor microenvironment, attract MSCs, and influence their biology...
December 2018: Immunity, Inflammation and Disease
EunJoo Chung, Yu Jung Kim, Myoung-Ro Lee, Shin-Hyeong Cho, Jung-Won Ju
INTRODUCTION: Clonorchis sinensis is a major parasite affecting the Korea population. Despite the high infection rate and pathogenicity, very few studies have been conducted to investigate the immune responses against the proteins of C. sinensis. METHODS: In this study, in vitro immune response induced by a recombinant 21.6 kDa tegumental protein derived from C. sinensis (rCsTegu21.6) was confirmed in murine dendritic cells and T cells. For the in vivo analysis, each mouse was immunized three times...
December 2018: Immunity, Inflammation and Disease
Melody Mazon, Valérie Larouche, Maryse St-Louis, Detlev Schindler, Madeleine Carreau
INTRODUCTION: Dickkopf-1 (DKK1) is a soluble protein and antagonist of the Wnt/β-catenin signaling pathway. DKK1 is found elevated in serum from patients affected with various types of cancers and in some instances, it is considered a diagnostic and prognostic biomarker. Elevated serum levels of DKK1 have also been detected in animal models of chronic inflammatory diseases. Previous work from our laboratory has demonstrated upregulation of DKK1 in cells and mouse models of the bone marrow failure (BMF) and cancer-prone disease Fanconi anemia (FA)...
December 2018: Immunity, Inflammation and Disease
Lau F Larsen, Nanna Juel-Berg, Anker Hansen, Kirsten S Hansen, E N Clare Mills, Ronald van Ree, Madeleine Rådinger, Lars K Poulsen, Bettina M Jensen
INTRODUCTION: Mast cells are the primary effector cells of allergy. This study aimed at characterizing human peripheral blood-derived mast cells (PBdMC) from peanut allergic and non-allergic subjects by investigating whether the molecular and stimulus-response profile of PBdMC discriminate between peanut allergic and healthy individuals. METHODS: PBdMC were generated from eight peanut allergic and 10 non-allergic subjects. The molecular profile (cell surface receptor expression) was assessed using flow cytometry...
December 2018: Immunity, Inflammation and Disease
Shiro Sonoda, Tetsuo Yamaguchi, Kotaro Aoki, Daisuke Ono, Ayami Sato, Chiaki Kajiwara, Soichiro Kimura, Yoshikiyo Akasaka, Yoshikazu Ishii, Yasunari Miyazaki, Naohiko Inase, Kazuhiro Tateda
INTRODUCTION: The USA300 clone of community-associated MRSA is reported to be hypervirulent and epidemic in the United States. This clone causes a variety of diseases from lethal pneumonia to mild skin infections. We hypothesized that evolutionary diversity may exist among USA300 clones, which may link virulence traits with host responses and mortality rates. METHODS: USA300 isolates from severe pneumonia (IP) and skin infection (IS) were characterized by pulsed-field gel electrophoresis (PFGE) and next-generation sequencing...
September 2018: Immunity, Inflammation and Disease
Keiji Oishi, Kazuto Matsunaga
INTRODUCTION: Recently, several new biological therapies targeted IgE and IL-5 in severe asthma have been developed and approved. In the last few years, there have been some reports on the therapeutic algorithms for severe asthmatic subjects screened by biomarkers. However, these algorithms have one problem. In atopic/eosinophilic overlapping asthmatic subjects, there is no effective answer to the question: "which is the optimal choice between Anti-IgE and anti-IL-5?" METHODS: We propose a new three-step algorithm for biological therapy in severe asthma...
September 2018: Immunity, Inflammation and Disease
Amy Y Liu, Stephen C De Rosa, Brandon L Guthrie, Robert Y Choi, Rose Kerubo-Bosire, Barbra A Richardson, James Kiarie, Carey Farquhar, Barbara Lohman-Payne
INTRODUCTION: Spontaneous interferon-γ (IFNγ) released detected by enzyme-linked immunospot (ELISpot) assays may be a biological phenomenon. Markers of immune activation levels were assessed as correlates of high background among individuals in Kenya. METHODS: Couples concordantly seronegative for HIV-1 were enrolled. IFN-γ ELISpot assays were conducted and negative control wells were categorized as having either high or low background (≥50 and <50 SFU/106 peripheral blood mononuclear cells [PBMC], respectively)...
September 2018: Immunity, Inflammation and Disease
S Gunnar O Johansson, Gunnar Lilja, Jenny Hallberg, Anna Nopp
INTRODUCTION: Omalizumab has been available for treatment of allergic asthma for more than a decade and thus, its efficacy in routine treatment was of interest to evaluate. Basophil allergen threshold sensitivity (CD-sens) has been shown to correlate with the bronchial allergen threshold sensitivity and can be used to objectively measure omalizumab treatment efficacy. We aimed to evaluate the effect of omalizumab treatment of allergic asthma by CD-sens, as an objective marker of the IgE-mediated inflammation, and related to SPT, spirometry, FeNO, Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE)...
September 2018: Immunity, Inflammation and Disease
Brian P Peppers, Anant Vatsayan, Jignesh Dalal, Tracey Bonfield, Haig Tcheurekdjian, Robert Hostoffer
INTRODUCTION: Anaphylaxis is a life threatening systemic inflammatory process that share mediators involved in the coagulation cascade. Platelet activating factor, known to increase platelet aggregation, has also been implicated as an important mediator of anaphylaxis. Although other inflammatory reactions are associated with an increased risk of thrombosis, anaphylaxis is currently not reported as one of them. Furthermore the role platelets may have in the perianaphylaxis period is not well understood...
September 2018: Immunity, Inflammation and Disease
Noémie Boillat-Blanco, Anneth-Mwasi N Tumbo, Matthieu Perreau, Patrizia Amelio, Kaushik L Ramaiya, Maliwaza Mganga, Christian Schindler, Sebastien Gagneux, Klaus Reither, Nicole Probst-Hensch, Giuseppe Pantaleo, Claudia Daubenberger, Damien Portevin
INTRODUCTION: The rising prevalence of Diabetes mellitus (DM) in high TB-endemic countries may adversely affect sustainability of TB control since DM constitutes a risk factor for development of active tuberculosis (TB). The impact of DM on TB specific adaptive immune responses remains poorly addressed, particularly in people living in Sub-Saharan countries. We performed a functional characterization of TB specific cellular immune response in Tanzanian subjects with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by their diabetic status...
June 2018: Immunity, Inflammation and Disease
Loretta G Que, Zhonghui Yang, Njira L Lugogo, Rohit K Katial, Steven A Shoemaker, Janice M Troha, David M Rodman, Robert M Tighe, Monica Kraft
RATIONALE: Patients with asthma demonstrate depletion of the endogenous bronchodilator GSNO and upregulation of GSNOR. OBJECTIVES: An exploratory proof of concept clinical study of N6022 in mild asthma to determine the potential bronchoprotective effects of GSNOR inhibition. Mechanistic studies aimed to provide translational evidence of effect. METHODS: Fourteen mild asthma patients were treated with intravenous N6022 (5 mg) or placebo and observed for 7 days, with repeated assessments of the provocative dose of methacholine causing a 20% fall in FEV1 (methacholine PC20 FEV1), followed by a washout period and crossover treatment and observation...
June 2018: Immunity, Inflammation and Disease
Jeansun Lee, Nele M G Dieckmann, James R Edgar, Gillian M Griffiths, Richard M Siegel
INTRODUCTION: T cell and NK cell cytotoxicity can be mediated via the perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a type II transmembrane protein that binds its cognate receptor Fas (CD95). Membrane-bound FasL is expressed on the plasma membrane of activated lymphocytes and is the main form of FasL with cytotoxic activity, but whether FasL is delivered to the immune synapse along with granzyme and perforin-containing granules is unclear. METHODS: We stably expressed FasL-fluorescent fusion proteins into human NK cells and examined the localization of FasL relative to other intracellular markers by confocal and immunoelectron microscopy, and examined the trafficking of FasL during formation of immune synapses with HLA-deficient B cells...
June 2018: Immunity, Inflammation and Disease
Clemens Wülfing, Fenja Amrei Schuran, Julia Urban, Jasmin Oehlmann, Hauke Simon Günther
INTRODUCTION: Recently, we found abundant innervation of antigen presenting cells that were reached and enclosed by single neurites. These neurally hard-wired antigen presenting cells (wAPC) could be observed in the T-cell zone of superficial cervical lymph nodes of rats and other mammalians, including humans. METHODS: As a consequence, we investigated lymph nodes at many different anatomical positions as well as all primary and secondary lymphoid organs (SLO) in rodents for a similar morphology of innervation regarding antigen presenting cells known in those tissues...
June 2018: Immunity, Inflammation and Disease
Sujata Prasad, Shuxian Hu, Wen S Sheng, Priyanka Chauhan, James R Lokensgard
INTRODUCTION: Previous work from our laboratory has demonstrated in vivo persistence of CD103+ CD69+ brain resident memory CD8+ T-cells (bTRM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these TRM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. METHODS: We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8+ T-cells obtained from wild type mice to investigate the role of glial cells in the development of bTRM ...
June 2018: Immunity, Inflammation and Disease
Evan Li, Chu-Lin Tsai, Zahida K Maskatia, Ekta Kakkar, Paul Porter, Roger D Rossen, Sarah Perusich, John M Knight, Farrah Kheradmand, David B Corry
INTRODUCTION: Fungal airway infection (airway mycosis) is increasingly recognized as a cause of asthma and related disorders. However, prior controlled studies of patients treated with antifungal antibiotics have produced conflicting results. Our objective is to measure the effect of antifungal therapy in moderate to severe adult asthmatics with positive fungal sputum cultures in a single center referral-based academic practice. METHODS: We retrospectively evaluated 41 patients with asthma and culture-proven airway mycosis treated with either terbinafine, fluconazole, itraconazole, voriconazole, or posaconazole for 4 to >12 weeks together with standard bronchodilator and anti-inflammatory agents...
June 2018: Immunity, Inflammation and Disease
Jihui Zhang, Jie Chen, Shannon C Mangat, Chathuri Perera Baruhupolage, David R Garrod, Clive Robinson
INTRODUCTION: Intracellular reactive oxidant species (ROS) are generated in human airway epithelial cells by the prothrombinase action of Group 1 house dust mite (HDM) allergens and by ligation of viral RNA sensor Toll-like receptors (TLRs). We explored signaling convergence between HDM allergens and TLRs in ROS generation because epithelial cells form the primary barrier against inhaled substances and dictate host responses to allergens and viruses. METHODS: ROS formation by Calu-3 human airway cells was studied by measuring dihydrorhodamine 123 oxidation after activation by polyinosinic:polycytidylic acid (to activate TLR3), CL097 (to activate TLR7), a natural mixture of HDM allergens, or BzATP...
June 2018: Immunity, Inflammation and Disease
Jarkko Mäntylä, Tuuli Thomander, Auli Hakulinen, Kaarina Kukkonen, Kati Palosuo, Helena Voutilainen, Anna Pelkonen, Paula Kauppi
INTRODUCTION: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. OBJECTIVE: We aimed to study if OIT is possible in adults. METHODS: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT...
June 2018: Immunity, Inflammation and Disease
David Ferrandiz-Mont, Nur Wahyuniati, Hsin-Jen Chen, Mulyadi Mulyadi, Tjut Mariam Zanaria, Dar-Der Ji
INTRODUCTION: Exact etiology and proper treatment of eczema are still unknown. The hygiene hypothesis and epidermal barrier dysfunction hypothesis attempted to give some plausible explanations for these issues but they still remain unclear. The identification of factors, including hygiene practices, related to eczema symptoms (ES) could shed some light on these matters. Therefore, this study aimed to determine risk factors related to ES and the ES prevalence in two disparate areas in terms of urbanization in Aceh, Indonesia...
June 2018: Immunity, Inflammation and Disease
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