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Clinical and Experimental Immunology

Tor Henrik Anderson Tvedt, Randi Hovland, Galina Tsykunova, Aymen Bushra Ahmed, Tobias Gedde-Dahl, Øystein Bruserud
BACKGROUND: Interleukin 6 (IL-6) is an important regulator of immunity and inflammation in many diseases. Single nucleotide polymorphisms (SNPs) in the IL-6 gene influence outcome after allogeneic stem cell transplantation (ASCT), but the possible importance of SNPs in the IL-6 receptor has not been examined. We therefore investigated whether SNPs in the IL-6R gene influenced biochemical characteristics and clinical outcomes after ASCT. PATIENTS AND METHODS: We investigated the IL-6 promoter variant rs1800975 and the IL-6R SNPs rs4453032, rs2228145, rs4129267, rs4845374, rs4329505, rs4845617, rs12083537, rs4845618, rs6698040 and rs4379670 in a 101 population-based cohort of allotransplant recipients and their family donors...
March 7, 2018: Clinical and Experimental Immunology
Akiyuki Uzawa, Masahiro Mori, Hiroki Masuda, Ryohei Ohtani, Tomohiko Uchida, Satoshi Kuwabara
Recombinant thrombomodulin (rTM) has pleiotropic properties including anti-coagulation and anti-inflammation; however, its effectiveness as a treatment for multiple sclerosis (MS) has not been fully evaluated. High mobility group box 1 (HMGB1) and pro-inflammatory cytokines, working as an inflammatory mediator, are reportedly involved in the inflammatory pathogenesis of MS. The aim of this study was to determine whether rTM can be a potential therapeutic agent for experimental autoimmune encephalomyelitis (EAE)...
March 6, 2018: Clinical and Experimental Immunology
Michael R Pranzatelli, Tyler J Allison, Nathan R McGee, Elizabeth D Tate
Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, especially due to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in pediatric neuroinflammation, we immunophenotyped CSF and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurologic disorders (NIND), 312 with opsoclonus-myoclonus (OMS), and 23 with other inflammatory neurologic disorders (OIND)...
February 27, 2018: Clinical and Experimental Immunology
Wencheng Su, Liping Du, Shengyun Liu, Jing Deng, Qinfeng Cao, Gangxiang Yuan, Aize Kijlstra, Peizeng Yang
Previous studies show that ERAP1/ERAP2 and RUNX3 gene polymorphisms are associated with AS (ankylosing spondylitis) in European Caucasians. However, contradictory results were reported in different Asian populations. Purpose of this study was to determine whether 11 candidate SNPs in ERAP1/ERAP2 and 6 in RUNX3 genes confer susceptibility to AS with or without AAU (AS+ AAU+ or AS+ AAU- ) in Chinese Han. Therefore, a case-control association study was performed in 882 AS+ AAU- , 884 AS+ AAU+ and 1727 healthy controls...
February 26, 2018: Clinical and Experimental Immunology
Lara A Aqrawi, Margarita Ivanchenko, Albin Björk, Jorge I Ramírez Sepúlveda, Juliana Imgenberg-Kreuz, Marika Kvarnström, Philipp Haselmayer, Janicke Liaaen Jensen, Gunnel Nordmark, Karine Chemin, Kathrine Skarstein, Marie Wahren-Herlenius
Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. CXCR5 is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand CXCL13. We here aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay...
February 17, 2018: Clinical and Experimental Immunology
Sofie Eg Jørgensen, Mette Christiansen, Laura Barrett Ryø, Hans Henrik Gad, Jakob Gjedsted, Peter Staeheli, Jacob Giehm Mikkelsen, Merete Storgaard, Rune Hartmann, Trine Hyrup Mogensen
Influenza virus infection causes worldwide seasonal epidemics. Although influenza usually is a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in antiviral responses during influenza. However, IFN regulatory factor (IRF)7 deficiency is so far the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 Swine Flu pandemic...
February 17, 2018: Clinical and Experimental Immunology
Josefine Tecklenborg, David Clayton, Stefan Siebert, Shana M Coley
The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease...
February 17, 2018: Clinical and Experimental Immunology
Gareth W Jones, David G Hill, Anna Cardus Figueras, Simon A Jones
The cytokine interleukin (IL)-6 is a major therapeutic target for the treatment of various inflammatory and autoimmune diseases. While IL-6 receives considerable attention in studies of innate and adaptive immunity, the IL-6-related family member IL-27 is increasingly recognized for its effects on cellular proliferation, differentiation and leukocyte effector functions. Both cytokines activate responses in myeloid and stromal tissue cells where they direct the transition from innate to adaptive immunity. However, they are frequently identified as lymphokines that control responses in T cells and B cells...
February 13, 2018: Clinical and Experimental Immunology
B Gorovits, D J Baltrukonis, I Bhattacharya, M A Birchler, D Finco, D Sikkema, M S Vincent, S Lula, L Marshall, T P Hickling
OBJECTIVE: To examine the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-TNF monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes. METHODS: Using findings of a recent systematic literature review of the immunogenicity of 11 biologic/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-tumor necrosis factor adalimumab and infliximab...
February 12, 2018: Clinical and Experimental Immunology
Aizhan Kozhakhmetova, Rebecca C Wyatt, Claire Caygill, Claire Williams, Anna E Long, Kyla Chandler, Rachel J Aitken, Janet M Wenzlau, Howard W Davidson, Kathleen M Gillespie, Alistair J K Williams
Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA), and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterised population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available...
February 12, 2018: Clinical and Experimental Immunology
Marie-Nicole Theodoraki, Thomas K Hoffmann, Theresa L Whiteside
Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumor- or T cell-derived exosomes in patient's plasma are immunosuppressive and impact on disease activity, we separated CD3(-) from CD3(+) exosomes by immunocapture using anti-CD3 Abs. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry...
February 12, 2018: Clinical and Experimental Immunology
Réka Kugyelka, Zoltán Kohl, Katalin Olasz, Lilla Prenek, Tímea Berki, Péter Balogh, Ferenc Boldizsár
The tyrosine kinase ZAP-70 (zeta-chain associated protein of 70 kDa) plays a key role in T cell development and signaling. In the absence of ZAP-70, T cell development is arrested in the CD4+ CD8+ double positive stage, thus ZAP-70 homozygous knockout (ZAP-70-/- ) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency. We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70-/- mice. We used a single intraperitoneal (ip...
February 12, 2018: Clinical and Experimental Immunology
Maha F Saja, H Terence Cook, Marieta M Ruseva, Marta Szajna, Matthew C Pickering, Kevin J Woollard, Marina Botto
Hyperlipidemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalised metabolic derangements. Under both situations, the lipid profile is characterised by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is increasingly recognised as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using the poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model...
February 6, 2018: Clinical and Experimental Immunology
Lukas Wisgrill, Isabelle Wessely, Andreas Spittler, Elisabeth Förster-Waldl, Angelika Berger, Kambis Sadeghi
Bioactive components of human milk such as human lactoferrin (hLF) play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a pro-inflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte-derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF and differentiation, apoptosis and phagocytosis were evaluated...
February 2, 2018: Clinical and Experimental Immunology
Kazuhisa Ouhara, Syuichi Munenaga, Mikihito Kajiya, Katsuhiro Takeda, Shinji Matsuda, Yoko Sato, Yuta Hamamoto, Tomoyuki Iwata, Satoshi Yamasaki, Keiichi Akutagawa, Noriyoshi Mizuno, Tsuyoshi Fujita, Eiji Sugiyama, Hidemi Kurihara
RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-UTR region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus, some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathognic bacteria. The involvement of HuR in the progression of PD was assessed using in vitro and in vivo experiment...
February 2, 2018: Clinical and Experimental Immunology
Panrawee Phoomvuthisarn, Andrew Cross, Laurence Glennon-Alty, Helen L Wright, Steven W Edwards
Human neutrophils are terminally-differentiated cells that do not replicate and yet express a number of enzymes, notably cell cycle-dependent kinases (CDKs) that are normally associated with control of DNA synthesis and cell cycle progression. In neutrophils, CDKs appear to function mostly to regulate apoptosis, although the mechanisms by which they regulate this process are largely unknown. Here we show that the CDK2 inhibitor, Purvalanol A induces a rapid decrease in Mcl-1 levels in human neutrophils and peripheral blood mononuclear cells (PBMCs), but only induces apoptosis in neutrophils which are dependent on expression on this protein for survival...
January 29, 2018: Clinical and Experimental Immunology
Jun Niu, Zhifang Zhai, Fei Hao, Yuancheng Zhang, Zhiqiang Song, Hua Zhong
CD3+ CD20+ T cells are a population of CD3+ T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. Here, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3+ CD20+ T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3+ T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors...
January 29, 2018: Clinical and Experimental Immunology
Caroline Evans, Elizabeth Bateman, Rachael Steven, Mark Ponsford, Alice Cullinane, Claire Shenton, Gillian Duthie, Chris Conlon, Stephen Jolles, Aarnoud P Huissoon, Hilary J Longhurst, Tasneem Rahman, Chris Scott, Gregg Wallis, Stephen Harding, Antony R Parker, Berne L Ferry
Vaccine specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, maybe an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multicentre study describing the analytical and clinical performance of a Typhi Vi IgG ELISA calibrated to an affinity purified Typhi Vi IgG preparation...
January 29, 2018: Clinical and Experimental Immunology
Yun Seon Kim, Mi Na Kim, Kyung Eun Lee, Jung Yeon Hong, Mi Seon Oh, Soo Yeon Kim, Kyung Won Kim, Myung Hyun Sohn
Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leukocyte cell adhesion molecule (ALCAM/CD166), on the surface of antigen presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were intraperitoneally sensitized with and orally fed OVA...
January 24, 2018: Clinical and Experimental Immunology
Greg Hodge, Sandra Hodge, Phan Tien Nguyen, Aeneas Yeo, Parama Sarkar, Arash Badiei, C L Holmes-Liew, Paul N Reynolds, Mark Holmes
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant...
January 20, 2018: Clinical and Experimental Immunology
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