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Clinical & Translational Immunology

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https://www.readbyqxmd.com/read/29333270/lessons-from-ten-years-of-genome-wide-association-studies-of-asthma
#1
REVIEW
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P<5 × 10-8, including 31 in populations of European ancestry. Results from analyses of the UK Biobank data (n=380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333269/the-immune-system-of-the-liver-50-years-of-strangeness
#2
EDITORIAL
Michaela Lucas, Axel Kallies, Paul Klenerman
No abstract text is available yet for this article.
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333268/progress-of-genome-wide-association-studies-of-ankylosing-spondylitis
#3
REVIEW
Zhixiu Li, Matthew A Brown
Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily affects the spine and sacroiliac joints. Significant progress has been made in discovery of genetic associations with AS by genome-wide association studies (GWAS) over past decade. These findings have uncovered novel pathways involved pathogenesis of the disease and have led to introduction of novel therapeutic treatments for AS. In this Review, we discuss the genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS-associated variations and critical cell types involved in AS development...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333267/type-1-diabetes-genome-wide-association-studies-not-to-be-lost-in-translation
#4
REVIEW
Flemming Pociot
Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case-control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#5
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29201362/a-generalized-quantitative-antibody-homeostasis-model-maintenance-of-global-antibody-equilibrium-by-effector-functions
#6
József Prechl
The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]=KD...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29114389/adoptive-cell-therapy-with-cd4-t-helper-1-cells-and-cd8-cytotoxic-t-cells-enhances-complete-rejection-of-an-established-tumour-leading-to-generation-of-endogenous-memory-responses-to-non-targeted-tumour-epitopes
#7
Kunyu Li, Braeden Donaldson, Vivienne Young, Vernon Ward, Christopher Jackson, Margaret Baird, Sarah Young
The results of adoptive T-cell therapies (ACTs) are very encouraging and show clinical evidence that ACT can provide a cure for patients with metastatic disease. However, various response rates and long-term cancer remission have been observed in different ACT trials. The types of T cells, prior treatment with chemotherapy and co-administration of other immune-target therapies have been found to influence the efficacy of ACT. In this study, we investigate the ability of ACT using CD4(+) T helper 1 (Th1) cells and CD8(+) cytotoxic T lymphocytes (CTLs) to reject the growth of established B16-ovalbumin (OVA) melanoma...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#8
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29114387/repeat-pneumococcal-polysaccharide-vaccination-does-not-impair-functional-immune-responses-among-indigenous-australians
#9
Paul V Licciardi, Edwin Hoe, Zheng Quan Toh, Anne Balloch, Sarah Moberley, Paula Binks, Rachel Marimla, Amanda Leach, Sue Skull, Kim Mulholland, Ross Andrews
Indigenous Australians experience one of the highest rates of pneumococcal disease globally. In the Northern Territory of Australia, a unique government-funded vaccination schedule for Indigenous Australian adults comprising multiple lifetime doses of the pneumococcal polysaccharide vaccine is currently implemented. Despite this programme, rates of pneumococcal disease do not appear to be declining, with concerns raised over the potential for immune hyporesponse associated with the use of this vaccine. We undertook a study to examine the immunogenicity and immune function of a single and repeat pneumococcal polysaccharide vaccination among Indigenous adults compared to non-Indigenous adults...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29114386/suppression-of-inflammation-and-tissue-damage-by-a-hookworm-recombinant-protein-in-experimental-colitis
#10
Ivana B Ferreira, Darren A Pickering, Sally Troy, John Croese, Alex Loukas, Severine Navarro
Gastrointestinal parasites, hookworms in particular, have evolved to cause minimal harm to their hosts when present in small numbers, allowing them to establish chronic infections for decades. They do so by creating an immunoregulatory environment that promotes their own survival, but paradoxically also benefits the host by protecting against the onset of many inflammatory diseases. To harness the therapeutic value of hookworms without using live parasites, we have examined the protective properties of the recombinant protein anti-inflammatory protein (AIP)-1, secreted in abundance by hookworms within the intestinal mucosa, in experimental colitis...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28983404/functional-heterogeneity-of-gut-resident-regulatory-t-cells
#11
REVIEW
Maik Luu, Ulrich Steinhoff, Alexander Visekruna
Regulatory T cells (Treg cells) have a central role in the maintenance of intestinal homeostasis by restraining inappropriate immune responses in the healthy gut. Although distinct intestinal immune cell populations have been described to exhibit regulatory activity, several genetic and functional studies provided a strong evidence for a pivotal role of forkhead box P3 (Foxp3)(+)CD4(+) Treg cells in prevention of dysregulated mucosal immune reactions and development of chronic immunological disorders such as celiac disease, food allergies and inflammatory bowel disease...
September 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28983403/autoimmunity-inflammation-in-a-monogenic-primary-immunodeficiency-cohort
#12
William Rae, Daniel Ward, Christopher J Mattocks, Yifang Gao, Reuben J Pengelly, Sanjay V Patel, Sarah Ennis, Saul N Faust, Anthony P Williams
Primary immunodeficiencies (PIDs) are rare inborn errors of immunity that have a heterogeneous phenotype that can include severe susceptibility to life-threatening infections from multiple pathogens, unique sensitivity to a single pathogen, autoimmune/inflammatory (AI/I) disease, allergies and/or malignancy. We present a diverse cohort of monogenic PID patients with and without AI/I diseases who underwent clinical, genetic and immunological phenotyping. Novel pathogenic variants were identified in IKBKG, CTLA4, NFKB1, GATA2, CD40LG and TAZ as well as previously reported pathogenic variants in STAT3, PIK3CD, STAT1, NFKB2 and STXBP2...
September 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28983402/regulatory-t-cell-heterogeneity-and-the-cancer-immune-response
#13
REVIEW
Kirsten A Ward-Hartstonge, Roslyn A Kemp
The frequency of circulating or tumour-infiltrating regulatory T cells (Tregs) has been associated with poor patient survival in many cancers including breast, melanoma and lung. It has been hypothesised that Tregs impact the anti-tumour function of effector T cells, resulting in worse outcomes for patients. However, high infiltrates of Tregs have been associated with a positive outcome of patients in a minority of cancers including colorectal, bladder and oesophageal. In addition, many studies have shown no impact of Tregs in patient outcome...
September 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28868144/inhibition-of-il-17a-by-secukinumab-shows-no-evidence-of-increased-mycobacterium-tuberculosis-infections
#14
Michael Kammüller, Tsen-Fang Tsai, Christopher Em Griffiths, Nidhi Kapoor, Pappachan E Kolattukudy, Dominique Brees, Salah-Dine Chibout, Jorge Safi, Todd Fox
Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis...
August 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28791126/investigation-of-sphingosine-kinase-1-in-interferon-responses-during-dengue-virus-infection
#15
Amanda L Aloia, Julie K Calvert, Jennifer N Clarke, Lorena T Davies, Karla J Helbig, Stuart M Pitson, Jillian M Carr
Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1(-)(/-) pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and -7 in SK1(-/-) pMEF...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28791125/nkg2c-memory-like-nk-cells-contribute-to-the-control-of-hiv-viremia-during-primary-infection-optiprim-anrs-147
#16
Françoise Gondois-Rey, Antoine Chéret, Samuel Granjeaud, Françoise Mallet, Ghislain Bidaut, Camille Lécuroux, Mickaël Ploquin, Michaela Müller-Trutwin, Christine Rouzioux, Véronique Avettand-Fenoël, Alessandro Moretta, Gilles Pialoux, Cécile Goujard, Laurence Meyer, Daniel Olive
Natural-killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C(+) NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C(+) NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART))...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28791124/combining-dendritic-cells-and-b-cells-for-presentation-of-oxidised-tumour-antigens-to-cd8-t-cells
#17
Melanie L Grant, Nicholas Shields, Silke Neumann, Katrin Kramer, Andrea Bonato, Christopher Jackson, Margaret A Baird, Sarah L Young
The dendritic cell (DC) is the foremost antigen-presenting cell (APC) for ex vivo expansion of tumour-specific patient T cells. Despite marked responses in some patients following reinfusion of DC-activated autologous or HLA-matched donor T cells, overall response rates remain modest in solid tumours. Furthermore, most studies aim to generate immune responses against defined tumour-associated antigens (TAA), however, meta-analysis reveals that those approaches have less clinical success than those using whole tumour cells or their components...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28748091/the-tetravalent-formulation-of-domain-iii-capsid-proteins-recalls-memory-b-and-t-cell-responses-induced-in-monkeys-by-an-experimental-dengue-virus-infection
#18
Lázaro Gil, Laura Lazo, Iris Valdés, Edith Suzarte, Phuong Yen, Rosa Ramírez, Mayling Álvarez, Le T Dung, Karem Cobas, Ernesto Marcos, Yusleidi Pérez, María G Guzmán, Ngyen D Hien, Gerardo Guillén, Lisset Hermida
Tetra DIIIC is a vaccine candidate against dengue virus (DENV) composed by four chimeric proteins that fuse the domain III of the envelope protein of each virus to the corresponding capsid protein. Containing B- and T-cell epitopes, these proteins form aggregates after the incubation with an immunostimulatory oligodeoxynucleotide, and their tetravalent formulation induces neutralizing antibodies and cellular immune response in mice and monkeys. Also, Tetra DIIIC protects mice after challenge with each DENV, and the monovalent formulation obtained from DENV-2 protects monkeys upon homologous viral challenge...
June 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28748090/erratum-defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#19
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
[This corrects the article DOI: 10.1038/cti.2016.87.].
June 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28695923/erratum-the-circulating-life-of-a-memory-t-follicular-helper-cell
#20
Cindy S Ma, Elissa K Deenick
[This corrects the article DOI: 10.1038/cti.2017.17.].
May 2017: Clinical & Translational Immunology
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