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Vikram Mehraj, Rayoun Ramendra, Stephane Isnard, Franck P Dupuy, Rosalie Ponte, Jun Chen, Ido Kema, Mohammad-Ali Jenabian, Cecilia Costiniuk, Bertrand Lebouché, Réjean Thomas, Pierre Coté, Roger Leblanc, Jean-Guy Baril, Madeleine Durand, Carl Chartrand-Lefebvre, Cécile Tremblay, Petronela Ancuta, Nicole F Bernard, Donald C Sheppard, Jean-Pierre Routy
BACKGROUND: Microbial translocation from the gut to circulation contributes to immune activation during HIV infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Gut fungal colonization increases during HIV infection and elevated systemic levels of the fungal polysaccharide (13)--D-Glucan (DG) have been reported in people living with HIV (PLWH). We assessed plasma DG in 146 early and chronic PLWH and investigated its contribution to systemic immune activation...
March 16, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Heather Wasik, Cozumel Pruette, Rebecca Ruebner, Mara McAdams-DeMarco, Sheng Zhou, Alicia Neu, Dorry Segev, Allan Massie
Pediatric kidney transplant (KT) candidates often have multiple potential living donors (LD); no evidence-based tool exists to compare potential LD, or to decide between marginal LD vs deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P-LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all-cause graft loss as a function of living donor characteristics and DD KDPI. HLA-B mismatch (aHR per mismatch=1.04 1.271.55 ), HLA-DR mismatch (aHR per mismatch=1...
March 15, 2019: American Journal of Transplantation
Abid Aljabri, Vijith Vijayan, Metodi Stankov, Christoph Nikolin, Constanca Figueiredo, Rainer Blasczyk, Jan Ulrich Becker, Andreas Linkermann, Stephan Immenschuh
Antibody-mediated rejection (AMR) is the major cause of allograft loss after solid organ transplantation. Circulating donor-specific antibodies against human leukocyte antigen (HLA), in particular HLA class II antibodies are critical for the pathogenesis of AMR via interactions with endothelial cells (ECs). To investigate the effects of HLA class II antibody ligation to the graft endothelium, a model of HLA-DR antibody-dependent stimulation was utilized in primary human ECs. Antibody ligation of HLA class II molecules in interferon-γ-treated ECs caused necrotic cell death without complement via a pathway that was independent of apoptosis and necroptosis...
March 8, 2019: Cell Death & Disease
Christina Hermanrud, Toni M M van Capel, Michael Auer, Virginija Karrenbauer, Florian Deisenhammer, Esther C de Jong, Anna Fogdell-Hahn
Interferon beta (IFNβ) is used as a first-line treatment for multiple sclerosis (MS) and is injected intramuscularly or subcutaneously (s.c.). The subcutaneous route is considered more immunogenic as it is associated with increased antidrug antibody-positive patients. The skin contains dendritic cells (DCs) and it is unclear whether these contribute to immunogenicity. To assess the effect of IFNβ on skin-resident cells, IFNβ was injected intradermally (i.d.) ex vivo using a human skin explant model or s...
March 8, 2019: Journal of Interferon & Cytokine Research
Vikram Mehraj, Rayoun Ramendra, Stéphane Isnard, Franck P Dupuy, Bertrand Lebouché, Cecilia Costiniuk, Réjean Thomas, Jason Szabo, Jean-Guy Baril, Benoit Trottier, Pierre Coté, Roger LeBlanc, Madéleine Durand, Carl Chartrand-Lefebvre, Ido Kema, Yonglong Zhang, Malcolm Finkelman, Cécile Tremblay, Jean-Pierre Routy
Background: CXCL13 is preferentially secreted by Follicular Helper T cells (TFH ) to attract B cells to germinal centers. Plasma levels of CXCL13 have been reported to be elevated during chronic HIV-infection, however there is limited data on such elevation during early phases of infection and on the effect of ART. Moreover, the contribution of CXCL13 to disease progression and systemic immune activation have been partially defined. Herein, we assessed the relationship between plasma levels of CXCL13 and systemic immune activation...
2019: Frontiers in Immunology
Fatema Al-Rashed, Zunair Ahmad, Mina Amin Iskandar, Jaakko Tuomilehto, Fahd Al-Mulla, Rasheed Ahmad
BACKGROUND/AIMS: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes...
2019: Cellular Physiology and Biochemistry
Benjamin Petro, Dolores Mahmud, Simona Taioli, Amudha Ganapathy, Vitalyi Senyuk, Kazumi G Yoshinaga, Montha Suphangul, Damiano Rondelli, Nadim Mahmud
The limited number of hematopoietic stem cells (HSC) within a single unit of human cord blood currently limits its use as an alternate graft source. However, we have developed a strategy using 5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA), which expands transplantable HSC 7- to 10-fold. In our current studies, we have assessed the allostimulatory capacity of the 5azaD/TSA-expanded grafts. The coexpression of immunophenotypic dendritic cell (DC) markers, such as HLA-DR/CD86 and HLA-DR/CD11c as determined by flow cytometry, and the allostimulatory capacity of 5azaD/TSA-expanded cells as determined by MLC were both significantly lower than control...
March 6, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Gaëlle Dzangué-Tchoupou, Kuberaka Mariampillai, Loïs Bolko, Damien Amelin, Wladimir Mauhin, Aurélien Corneau, Catherine Blanc, Yves Allenbach, Olivier Benveniste
BACKGROUND: Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious. OBJECTIVES: Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers...
February 27, 2019: Autoimmunity Reviews
Kelly L Damm-Ganamet, Nidhi Arora, Stephane Becart, James Patrick Edwards, Alec D Lebsack, Heather McAllister, Marina I Nelen, Navin Rao, Lori Westover, John J M Wiener, Taraneh Mirzadegan
At the onset of a drug discovery program, the goal is to identify novel compounds with appropriate chemical features that can be taken forward as lead series. Here, we describe three prospective case studies, Bruton Tyrosine Kinase (BTK), RAR-Related Orphan Receptor γ t (RORγt) and Human Leukocyte Antigen DR isotype (HLA-DR) to illustrate the positive impact of high throughput virtual screening (HTVS) on the successful identification of novel chemical series. Each case represents a project with a varying degree of difficulty due to the amount of structural and ligand information available internally or in the public domain to utilize in the virtual screens...
February 28, 2019: Journal of Chemical Information and Modeling
Arunachalam Ramaiah, Soumya Nayak, Srabanti Rakshit, Abigail L Manson, Thomas Abeel, Sivakumar Shanmugam, Pravat Nalini Sahoo, Anto Jesuraj Uday Kumar John, Jagadish Chandrabose Sundaramurthi, Sujatha Narayanan, George D'Souza, Paul von Hoegen, Tom H M Ottenhoff, Soumya Swaminathan, Ashlee M Earl, Annapurna Vyakarnam
Vaccines that confer protection through induction of adaptive T-cell immunity rely on understanding T-cell epitope (TCE) evolution induced by immune escape. This is poorly understood in tuberculosis (TB), an ancient, chronic disease, where CD4 T-cell immunity is of recognized importance. We probed 905 functionally validated, curated human CD4 T cell epitopes in 79 Mycobacterium tuberculosis (Mtb) whole genomes from India. This screen resulted in identifying 64 mutated epitopes in these strains initially using a computational pipeline and subsequently verified by single nucleotide polymorphism (SNP) analysis...
2019: Frontiers in Immunology
Marion Pardons, Amy E Baxter, Marta Massanella, Amélie Pagliuzza, Rémi Fromentin, Caroline Dufour, Louise Leyre, Jean-Pierre Routy, Daniel E Kaufmann, Nicolas Chomont
The phenotypic characterization of the cells in which HIV persists during antiretroviral therapy (ART) remains technically challenging. We developed a simple flow cytometry-based assay to quantify and characterize infected cells producing HIV proteins during untreated and treated HIV infection. By combining two antibodies targeting the HIV capsid in a standard intracellular staining protocol, we demonstrate that p24-producing cells can be detected with high specificity and sensitivity in the blood from people living with HIV...
February 27, 2019: PLoS Pathogens
Raquel Almansa, Silvia Martín, Marta Martin-Fernandez, María Heredia-Rodríguez, Esther Gómez-Sánchez, Marta Aragón, Cristina Andrés, Dolores Calvo, Jesus Rico-Feijoo, Maria Carmen Esteban-Velasco, Luis Mario Vaquero-Roncero, Alicia Ortega, Estefania Gómez-Pesquera, Mario Lorenzo-López, Iñigo López de Cenarruzabeitia, Diana Benavides, Jaime López-Sanchez, Cristina Doncel, Carmen González-Sanchez, Esther Zarca, Alberto Ríos-Llorente, Agustín Diaz, Elisa Sanchez-Barrado, Juan Beltran de Heredia, Jose Maria Calvo-Vecino, Luis Muñoz-Bellvís, Jose Ignacio Gomez-Herreras, César Aldecoa, Eduardo Tamayo, Jesus F Bermejo-Martin
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
February 27, 2019: Scientific Reports
Pomme Bm Poppelaars, Lilian H D van Tuyl, Maarten Boers
OBJECTIVES: Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population. METHODS: The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression...
February 26, 2019: Annals of the Rheumatic Diseases
Mohamed I M Ahmed, Christian Ziegler, Kathrin Held, Ilja Dubinski, Julia Ley-Zaporozhan, Christof Geldmacher, Ulrich von Both
Tuberculosis (TB) epidemiology is changing in Western and Central Europe due to the rise in immigration and refugees fleeing high-TB-burden areas of war and devastation. The change in local demography and the lack of sensitive and specific TB diagnostic and monitoring tools, especially for cases of childhood TB, leads to either missed cases or over-treatment of this group. Here we present a promising new diagnostic approach, the T cell activation marker (TAM)-TB assay, and its performance in a case of extra-pulmonary TB occurring in a 16 year old refugee from Afghanistan...
2019: Frontiers in Pediatrics
C H Jia, L Wang, F H Jing, J Xie, Z F Qiu, T S Li, W Lyu
Objective: To investigate the clinical features and T lymphocytes subsets in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) infection. Methods: A total of 48 hospitalized patients with human immunodeficiency virus (HIV)-1/AIDS and CMV infections were recruited at Peking Union Medical College Hospital from Jan 2010 to Aug 2017. Their clinical features and immune function were retrospectively analyzed. Patients with only HIV/AIDS in previous study were recruited as controls...
March 1, 2019: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
B C Buerfent, L Gölz, A Hofmann, H Rühl, W Stamminger, N Fricker, T Hess, J Oldenburg, M M Nöthen, J Schumacher, M P Hübner, A Hoerauf
Filarial nematodes modulate immune responses in their host to enable their survival and mediate protective effects against autoimmunity and allergies. In this study, we examined the immunomodulatory capacity of extracts from the human pathogenic filaria Brugia malayi (BmA) on human monocyte responses in a transcriptome-wide manner to identify associated pathways and diseases. As previous transcriptome studies often observed quiescent responses of innate cells to filariae, the potential of BmA to alter LPS driven responses was investigated by analyzing >47...
February 22, 2019: Scientific Reports
Bin Li, Tie-Niu Song, Fu-Rong Wang, Ci Yin, Zheng Li, Jun-Ping Lin, Yu-Qi Meng, Hai-Ming Feng, Tao Jing
Macrophages constitute one of the most common components of immune cells, which penetrate tumors and they have a key role in tumor prognosis. Here, we identified an unrecognized macrophage subpopulation, which favors tumorigenesis. These macrophages express programmed cell death protein 1 (PD1) in a constitutive manner and accumulates in esophageal squamous cell carcinoma (ESCC) in advanced stage of the disease and is negatively associated with the survival of ESCC patients. The PD1+ tumor-associated macrophages (PD1+ TAMs) displayed surface pattern and function akin to M2: a substantial enhancement in CD206 and IL-10 expression; a specific reduction in HLA-DR, CD64, and IL-12 expression; and a significant increase in the ability to inhibit CD8+ T-cell proliferation...
February 22, 2019: Oncogenesis
Ilaria Russo, Chiara Del Giorno, Ivana Giangrieco, Najla Hajji, Maria Antonietta Ciardiello, Paola Iovino, Carolina Ciacci
OBJECTIVE: Celiac disease is an immune-mediated disease of the intestine triggered by gluten. Gluten elicits, in genetically susceptible individuals, cytokine responses that are then transmitted to the immunocompetent cells. Vegetables and fruit have anti-inflammatory and antioxidant properties with a protective effect on intestinal epithelium. Kiwifruit is known to have beneficial effects on the intestinal tissues, and it is the only plant food containing the peptide kissper, with anti-inflammatory properties...
February 22, 2019: Journal of the American College of Nutrition
Tanya Debnath, Lakshmi Kiran Chelluri
Background: Mesenchymal stem cells have immense potential in stem cell-based therapies, however there is a pre-requisite to develop a curative cell dose. Adipose tissue-derived mesenchymal stem cells are promising mainly due to their potential abundance, immunomodulatory effect and remarkable differentiation potential. Nevertheless, senescence may develop during their in vitro expansion due to the incidence of genetic instability. Hence, it is important to attain an ideal balance between mesenchymal stem cell growth, quality and genetic integrity before their clinical use...
January 2019: Hematology, Transfusion and Cell Therapy
Neda Djedovic, María José Mansilla, Bojan Jevtić, Juan Navarro-Barriuso, Tamara Saksida, Eva M Martínez-Cáceres, Ðorđe Miljković
Dendritic cells (DC) are professional antigen presenting cells that have a key role in shaping the immune response. Tolerogenic DC (tolDC) have immuno-regulatory properties and they are a promising prospective therapy for multiple sclerosis and other autoimmune diseases. Ethyl pyruvate (EP) is a redox analog of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that EP ameliorates experimental autoimmune encephalomyelitis, a multiple sclerosis murine model. Here, we expanded our study to its tolerogenic effects on DC...
2019: Frontiers in Immunology
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