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Clinical and Experimental Immunology

Jeremy Woodward, Effrossyni Gkrania-Klotsas, Dinakantha Kumararatne
Chronic infection with Norovirus is emerging as a significant risk for patients with immunodeficiency - either primary or secondary to therapeutic immunosuppression. Patients with primary immunodeficiency present a range of pathological responses to Norovirus infection. Asymptomatic infections occur and differentiating viral carriage or prolonged viral shedding after self-limiting infection from infection causing protracted diarrhoea can be challenging due to relatively mild pathological changes that may mimic other causes of diarrhoea in such patients (for instance pathogenic bacteria or parasites or graft-versus-host disease)...
October 18, 2016: Clinical and Experimental Immunology
E Balada, L Felip, J Ordi-Ros, M Vilardell-Tarrés
We evaluated the transcriptional expression of DUSP23 in CD4+ T cells from 30 SLE patients and 30 healthy controls. DUSP23 mRNA levels were considerably higher in the patients group: 1,490 ± 1,713 versus 294,1 ± 204,2. None association was found between DUSP23 mRNA expression and the presence of typical serological and clinical parameters associated to SLE. Meaningful statistical values were obtained in the patients group between the levels of DUSP23 and ITGAL, PRF1, and CD40L. Similarly, transcript levels of different DNA methylation-related enzymes (DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4) were also positively correlated to the expression of DUSP23...
October 13, 2016: Clinical and Experimental Immunology
T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca(2+) ) cell signalling. Reduced TRPM3 has been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilisation has yet to be determined. Fifteen CFS/ME patients (mean age 48.82 ± 9.83 years) and 25 health controls (mean age 39.2 ± 12.12 years) were examined. Isolated NK cells were labelled with fluorescent antibodies to determine TRPM3, CD107a, and CD69 receptors on CD56(Dim) CD16(+) NK cells and CD56(Bright) CD16(Dim/-) NK cells...
October 11, 2016: Clinical and Experimental Immunology
Devin M Boe, Lisbeth A Boule, Elizabeth J Kovacs
The world is undergoing an unprecedented shift in demographics, with the number of individuals over the age of 60 projected to reach 2 billion or more by 2050, representing 22% of the global population. The elderly are at a higher risk for chronic disease and more susceptible to infection, due in part to age-related dysfunction of the immune system resulting from low-grade chronic inflammation known as "inflamm-aging". The innate immune system of older individuals exhibits a diminished ability to respond to microbial threats and clear infections, resulting in a greater occurrence of many infectious diseases in the elderly...
October 6, 2016: Clinical and Experimental Immunology
Priyanka Gaur, Arpita Myles, Ramnath Misra, Amita Aggarwal
Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with Enthesitis-related-arthritis (JIA-ERA) has shown the involvement of monocytes. On basis of CD14 and CD16 expression monocytes are classified as classical, intermediate and non-classical. In response to Toll-like Receptor (TLR) stimulation intermediate-monocytes produce pro-inflammatory cytokines and play a role in inflammatory diseases. Thus we have studied the microarray profile of monocytes, frequency of their subsets and cytokine production...
October 5, 2016: Clinical and Experimental Immunology
Shu-Hui Chen, Qiao-Li Lv, Lei Hu, Ming-Jing Peng, Gui-Hua Wang, Bao Sun
Although lupus is, by definition, associated with genetic and immunological factors, its molecular mechanisms remain unclear. The up-to-date research findings point out that various genetic and epigenetic factors, especially gene-specific and site-specific methylation, are believed to contribute to the initiation and development of systemic lupus erythematosus (SLE). This review presents and summarizes the association between abnormal DNA methylation of immune-related cells and lupus-like diseases, as well as the possible mechanisms of immune disorder caused by DNA methylation, aiming at a better understanding of the roles of aberrant DNA methylation in the initiation and development of certain forms of lupus and providing a new insight into promising therapeutic regimens in lupus-like diseases...
September 30, 2016: Clinical and Experimental Immunology
Arne N Akbar
Immunosurveillance requires the migration of lymphocytes and their activation to induce proliferation and effector function. Effective immunity requires an optimal supply of nutrients to lymphocytes. Cells contain nutrient sensing apparatus such as adenosine 5'-monophosphate-activated protein kinase (AMPK) that survey intracellular ATP levels. Immunity declines during ageing and one possibility is that the energy balance may be altered in old lymphocytes. This article summarizes recent data identifying a convergence of senescence and nutrient signalling pathways in lymphocytes that inhibit both T cell and NK cell function during ageing...
September 30, 2016: Clinical and Experimental Immunology
Vincent Hurez, Álvaro Padrón, Robert S Svatek, Tyler J Curiel
Immunotherapy is now experiencing unprecedented successes in treating various cancers based on new understandings of cancer immunopathogenesis. Nonetheless, although aging is the biggest risk factor for cancer, the majority of cancer immunotherapy preclinical studies are done in young hosts. This review will explore age-related changes in immunity as they relate to cancer immune surveillance, immunopathogenesis and responses to immunotherapy. Although it is recognized that declining T cell function with age poses a great challenge to developing effective age-related cancer immunotherapies, examples of successful approaches to overcome this hurdle have been developed...
September 30, 2016: Clinical and Experimental Immunology
Anderson P Jones, Allan G Kermode, Robyn M Lucas, William M Carroll, David Nolan, Prue H Hart
Circulating T and B lymphocytes contribute to the pathogenesis of the neuroinflammatory autoimmune disease, multiple sclerosis (MS). Further progress in the development of MS treatments is dependent upon a greater understanding of the immunological disturbances that underlie the disease. Analyses of circulating immune cells by flow cytometry have revealed MS-associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity. Disturbances in circulating immune populations reflect those observed in the central nervous system and include skewing towards proinflammatory CD4+ and CD8+ T cells and B cells, greater proportions of follicular T helper cells, and functional defects in the corresponding T and B regulatory subsets...
September 30, 2016: Clinical and Experimental Immunology
Juan Ignacio Basile, Denise Kviatcovsky, María Mercedes Romero, Luciana Balboa, Johana Monteserin, Viviana Ritacco, Beatriz Lopez, Carmen Sabio Y García, Ana García, Marisa Vescovo, Pablo González Montaner, Domingo Palmero, María Del Carmen Sasiain, Silvia de la Barrera
We have previously reported that T cells from patients with multidrug-resistant tuberculosis (MDR-TB) express high levels of IL-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M.tuberculosis). Herein, we explore the pathways involved in the induction of h17 cells in MDR-TB patients and healthy tuberculin reactors (PPD(+) HD) by the M strain and the laboratory strain H37Rv. Our results show that IL-1β and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17(+) IFNγ- and IL-17(+) IFNγ(+) in CD4(+) T cells from MDR-TB and PPD(+) HD...
September 28, 2016: Clinical and Experimental Immunology
Bakri M Assas, Scott Levison, Matthew Little, Hazel England, Laura Battrick, James Bagnall, John McLaughlin, Pawel Paszek, Kathryn J Else, Joanne L Pennock
Infliximab (IFX) has been used repeatedly in mouse pre-clinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse TNFα. However the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNFα was investigated ex vivo using ELISA, flow cytometry and western blot. IFX did not bind directly to soluble or membrane-bound mouse TNFα nor did it have any effect on TNFα-induced NfKb stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNFα independent T...
September 26, 2016: Clinical and Experimental Immunology
Amy E Anderson, David J Swan, Oi Yean Wong, Matthew Buck, Oliver Eltherington, Rachel A Harry, Angela M Patterson, Arthur G Pratt, Gary Reynolds, John-Paul Doran, John A Kirby, John D Isaacs, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T-cells. Lack of IL-12p70 production is a key immunoregulatory attribute of tolDC but does not fully explain their action. Here we show that tolDC express TGF-β1 at both mRNA and protein level, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC...
September 26, 2016: Clinical and Experimental Immunology
A Głobińska, M Pawełczyk, A Piechota-Polańczyk, A Olszewska-Ziąber, S Moskwa, A Mikołajczyk, A Jabłońska, P Zakrzewski, M Brauncajs, M Jarzębska, S Taka, N G Papadopoulos, M L Kowalski
PURPOSE: The aim of the study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. METHODS: NECs were obtained from 8 patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR3 and TLR7/8 agonists...
September 26, 2016: Clinical and Experimental Immunology
Amar Singh, Anant Mohan, Aprajit B Dey, Dipendra K Mitra
BACKGROUND: Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is key immune checkpoint receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to M. tuberculosis infection, leading to disseminated disease like miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathologic sites remains to be addressed...
September 26, 2016: Clinical and Experimental Immunology
M Tahara, H Tsuboi, S Segawa, H Asashima, M Iizuka-Koga, T Hirota, H Takahashi, Y Kondo, M Matsui, I Matsumoto, T Sumida
We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3(+) T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R(-/-) ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1(-/-) ) mice (M3R(-/-) →Rag-1(-/-) ) with MIS...
September 19, 2016: Clinical and Experimental Immunology
A A Anas, J Yang, J Daan de Boer, J J T H Roelofs, B Hou, A F de Vos, T van der Poll
Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model...
September 14, 2016: Clinical and Experimental Immunology
M Borte, G Kriván, B Derfalvi, L Maródi, T Harrer, S Jolles, C Bourgeois, W Engl, H Leibl, B McCoy, D Gelmont, L Yel
A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment...
September 10, 2016: Clinical and Experimental Immunology
E Apostolou, E K Kapsogeorgou, O D Konsta, I Giotakis, M I Saridaki, E Andreakos, A G Tzioufas
Type III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)-28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls...
September 10, 2016: Clinical and Experimental Immunology
C Montén, Å Torinsson Naluai, D Agardh
Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear factor kappa B (NF-κB) and interleukin (IL)-8 secretion or anti-inflammatory through epidermal growth factor receptors. NT mRNA is down-regulated in duodenal biopsies of children with untreated coeliac disease. The aim of this study was to investigate if plasma pro-NT levels correlated with the degree of intestinal mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children with coeliac disease. Fasting plasma samples from 96 children with coeliac disease and 89 non-coeliac disease controls were analysed for NT precursor fragment pro-NT 1-117 by a chemiluminometric immunoassay...
September 10, 2016: Clinical and Experimental Immunology
R R Montgomery
West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti-viral immune genes, but age is the most well-defined risk factor for susceptibility to severe disease...
September 10, 2016: Clinical and Experimental Immunology
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