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Clinical and Experimental Immunology

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https://www.readbyqxmd.com/read/29148078/soluble-tam-receptor-tyrosine-kinases-in-rheumatoid-arthritis-correlation-with-disease-activity-and-bone-destruction
#1
Liling Xu, Fanlei Hu, Huaqun Zhu, Xu Liu, Lianjie Shi, Yun Li, Hua Zhong, Su Yin
The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well-explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in the patients with RA. 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled in this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by ELISA, then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analyzed...
November 17, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29139554/immune-checkpoint-inhibitors-new-strategies-to-checkmate-cancer
#2
REVIEW
Ruairi A M Wilson, T R Jeffry Evans, Alasdair R Fraser, Robert J B Nibbs
Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging...
November 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29131315/txndc5-contributes-to-rheumatoid-arthritis-by-down-regulating-igfbp1-expression
#3
Jian Li, Bing Xu, Changsun Wu, Xinfeng Yan, Lei Zhang, Xiaotian Chang
The thioredoxin domain-containing 5 (TXNDC5) gene is associated with susceptibility to rheumatoid arthritis (RA) and exhibits increased expression in the synovial tissues. TXNDC5 is also strongly associated with diabetes, a metabolic disease characterized by interrupted insulin signaling. This study investigated whether TXNDC5 contributes to RA via the insulin signaling pathway. In the study, RA synovial fibroblast-like cells (RASFs) transfected with an anti-TXNDC5 small interfering RNA (siRNA) were analyzed with an Insulin Signaling Pathway RT(2) Profiler PCR Array and an Insulin Resistance RT(2) Profiler PCR Array...
November 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29114847/intestinal-anti-transglutaminase2-iga-deposits-in-children-at-risk-for-coeliac-disease-data-from-the-prevent-cd-study
#4
Melissa Borrelli, Mariantonia Maglio, Ilma R Korponay-Szabó, Viktória Vass, M Luisa Mearin, Caroline Meijer, Hagit Niv-Drori, Carmen Ribes-Koninckx, María Roca, Raanan Shamir, Riccardo Troncone, Renata Auricchio
In Coeliac Disease (CD) anti-tissue transglutaminase2 IgA antibodies(anti-TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European multicenter study, which studies the influence of infant nutrition, and that of genetic, immunologic and other environmental factors, on the risk of developing CD. The aim of the current study was to evaluate in very early intestinal biopsies from at-risk infants the appearance of intestinal anti-TG2 deposits and their predictive value for villous atrophy...
November 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29105068/activation-of-plasmacytoid-dendritic-cells-by-apoptotic-particles-mechanism-for-the-loss-of-immunologic-tolerance-in-sj%C3%A3-gren-s-syndrome
#5
Mari Ainola, Pauliina Porola, Yuya Takakubo, Beata Przybyla, Vesa-Petteri Kouri, Tuomas Aleksi Tolvanen, Arno Hänninen, Dan Christian Nordström
Sjögren's syndrome (SS) is a common autoimmune disease targeting salivary and lacrimal glands. It is strongly female-dominant characterized by low estrogen levels combined with a local intracrine dihydrotestosterone defect. We hypothesized that these hormonal deficits lead to increased apoptosis of the epithelial cells and plasmacytoid dendritic cell (pDC) mediated pro-inflammatory host responses. Expression of Toll-like receptors (TLRs) 7 and 9 and cytokine profile was studied in pDCs treated with apoptotic particles collected in consecutive centrifugation steps of media from apoptotic cells...
November 4, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29080328/clinical-and-functional-significance-of-steap4-splice-variant-in-cd14-monocytes-in-patients-with-rheumatoid-arthritis
#6
Hiroshi Ebe, Isao Matsumoto, Hoshimi Kawaguchi, Izumi Kurata, Yuki Tanaka, Asuka Inoue, Yuya Kondo, Hiroto Tsuboi, Takayuki Sumida
Tumor necrosis factor alpha (TNFα)-induced adipose-related protein (TIARP) is a negative regulator of inflammation in arthritis model mice. In humans, six transmembrane epithelial antigen of prostate 4 (STEAP4) (human counterpart of TIARP) is also expressed in CD14(+) monocytes from patients with rheumatoid arthritis (RA). Recently, highly levels of exon3-spliced variant STEAP4 (v-STEAP4) expression have been observed in porcine lung. The aim of this study is to elucidate the expression and functional role of v-STEAP4, comparing it with that of STEAP4, in the pathogenesis of arthritis...
October 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29058314/t-cell-suppression-in-the-bone-marrow-of-visceral-leishmaniasis-patients-impact-of-parasite-load
#7
Prabin Kumar, Pragya Misra, Chandreshwar Prasad Thakur, Abhinav Saurabh, Narayan Rishi, Dipendra Kumar Mitra
Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and Leishmania infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present study was focussed on parasite load with T cell function in bone marrow of twenty-six (26) VL patients. We observed significant enrichment of Foxp3(+) (p = 0.0003) and IL-10(+) Foxp3(+) T-regulatory (Treg) cells (p = 0...
October 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29058308/analysis-of-the-regulatory-function-of-nk-cells-from-patients-with-systemic-lupus-erythematosus
#8
Daniela De Jesús Cruz-González, Diana Gómez-Martin, Lourdes Baranda, Carlos Abud-Mendoza, Jorge Alcocer-Varela, Roberto González-Amaro, Adriana E Monsiváis-Urenda
Natural Killer cells (NK cells) participates in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analyzed the expression of NK receptors and costimulatory molecules in peripheral NK cells (CD3-CD56+) from SLE patients as well as the numbers of HLA-DR/CD11c+ NK cells...
October 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29058307/genetic-immunization-with-mouse-thyrotropin-hormone-receptor-plasmid-breaks-self-tolerance-for-a-murine-model-of-autoimmune-thyroid-disease-and-graves-orbitopathy
#9
Anke Schlüter, Mareike Horstmann, Salvador Diaz-Cano, Svenja Plöhn, Kerstin Stähr, Stefan Mattheis, Michael Oeverhaus, Stephan Lang, Ulrich Flögel, Utta Berchner-Pfannschmidt, Anja Eckstein, J Paul Banga
Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells...
October 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29052227/adjuvant-pretreatment-with-alum-protects-neonatal-mice-in-sepsis-through-myeloid-cell-activation
#10
Jaimar C Rincon, Angela L Cuenca, Steven L Raymond, Brittany Mathias, Dina C Nacionales, Ricardo Ungaro, Philip A Efron, James L Wynn, Lyle L Moldawer, Shawn D Larson
The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Especially in the premature neonate where outcomes from sepsis are so dismal, pretreatment strategies to prevent sepsis have received inadequate consideration. Aluminum-based adjuvants (alum) are currently used in many pediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pre-treatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis...
October 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29119559/preoperative-methylprednisolone-increases-plasma-pentraxin-3-early-after-total-knee-arthroplasty-a-randomized-double-blind-placebo-controlled-trial
#11
V Lindberg-Larsen, H Kehlet, K Pilely, J Bagger, M L Rovsing, P Garred
Preoperative glucocorticoid administration reduces the systemic inflammatory response. Pentraxin 3 (PTX3) is a novel inflammatory marker belonging to the humoral arm of innate immunity exerting a potentially protective host response. This study evaluated PTX3 and other complement marker changes after preoperative methylprednisolone (MP) early after total knee arthroplasty (TKA). Seventy patients were randomized (1 : 1) to preoperative intravenous (i.v.) MP 125 mg (group MP) or isotonic saline i.v. (group C)...
October 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29027667/co-inhibitory-profile-and-cytotoxicity-of-cd57-pd-1-t-cells-in-end-stage-renal-disease-patients
#12
Rens Kraaijeveld, Gretchen N de Graav, Marjolein Dieterich, Nicolle H R Litjens, Dennis A Hesselink, Carla C Baan
Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection as compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28(-) T-cells, which express CD57, are not susceptible to belatacept treatment. High number of CD4(+) CD57(+) PD-1(-) T-cells pre transplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of FACS-sorted CD4(+) CD57(+) PD-1(-) and CD8(+) CD57(+) PD-1(-) T-cells, and their CD57(-) control populations, after allo antigen stimulation...
October 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29023673/eppur-si-muove-ferritin-is-essential-in-modulating-inflammation
#13
Kassem Sharif, Vania Vieira Borba, Gisele Zandman-Goddard, Yehuda Shoenfeld
Ferritin, which was only discovered in the last century has stirred a formidable debate.. For long, Ferritin was appreciated as a non-specific acute phase reactant. Several years ago, we hypothesized the contributory role of ferritin as a pathogenic molecule rather than being a product of inflammation. Latest emerging evidence provide support to this notion. Such revelation provides a step forward toward the understanding of disease conditions associated with hyperferritenemia, and hence provide new targets for treatment modalities...
October 11, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28990652/bronchiectasis-and-deteriorating-lung-function-in-agammaglobulinaemia-despite-immunoglobulin-replacement-therapy
#14
A Stubbs, C Bangs, B Shillitoe, J D Edgar, S O Burns, M Thomas, H Alachkar, M Buckland, E McDermott, G Arumugakani, M S Jolles, R Herriot, P D Arkwright
Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinaemia. We hypothesized that despite regular immunoglobulin therapy, some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. One hundred and thirty-nine (70%) of 199 patients aged 1-80 years from nine cities in the United Kingdom with agammaglobulinaemia currently listed on the UK Primary Immune Deficiency (UKPID) registry were recruited into this retrospective case study and their clinical and laboratory features analysed; 94% were male, 78% of whom had Bruton tyrosine kinase (BTK) gene mutations...
October 9, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28987000/microrna-126-deficiency-enhanced-the-activation-and-function-of-cd4-t-cells-by-elevating-irs-1-pathway
#15
Fengyun Chu, Yan Hu, Ya Zhou, Mengmeng Guo, Jia Lu, Wen Zheng, Hualin Xu, Juanjuan Zhao, Lin Xu
Recent evidence showed that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4(+) T cells remains largely unknown. Here we firstly found that the activation and proliferation, as well as the expression of IFN-γ, of CD4(+) T cells from miR-126 knockdown (KD) mice using miRNA-Sponge technique were enhanced significantly in vitro, compared with those in CD4(+) T cells from wild type (WT) mice...
October 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28984923/b-cell-tolerance-to-epidermal-ribonuclear-associated-neo-autoantigen-in-vivo
#16
Søren E Degn, Elisabeth Alicot, Michael C Carroll
Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies in e.g. systemic lupus erythematosus (SLE) commonly have an intrinsic ability to engage not only the B cell receptor (BCR), but also a costimulatory pathway in B cells, such as the TLR7 pathway. Here we developed a novel mouse model displaying inducible expression of a fluorescent epidermal neo-autoantigen carrying an OT-II T cell epitope, B cell antigen, and associated ribonucleic acids capable of stimulating TLR7...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28984903/whole-genome-microarray-expression-analysis-in-blood-leucocytes-identifies-pathways-linked-to-signs-and-symptoms-of-a-patient-with-hypercalprotectinaemia-and-hyperzincaemia
#17
Helena S Isaksson, Sanja A Farkas, Patrick Müller, Dan Gustafsson, Torbjörn K Nilsson
A child, 2 yr with the "hypercalprotectinemia with hyperzincemia" clinical syndrome presented with atypical symptoms and signs, notably persistent fever of around 38°C, thrombocythaemia of >700 x 10(9) /L, and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analyzed whole-genome mRNA expression by the Affymetrix HG U133 PLUS 2.0 array on three occasions 3 to 5 months apart. Major upregulation was demonstrated for the JAK/STAT pathway including in particular CD177, S100A8, S100A9, and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors, and activators, accounting for the febrile apathic state; and the HMBG1 gene, possibly accounting for part of the intestinal symptoms...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28984901/truly-selective-primary-igm-deficiency-is-probably-very-rare
#18
L M A Janssen, T Macken, M C W Creemers, J F M Pruijt, J J J Eijk, E de Vries
Isolated decreased serum-immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and analysing retrospectively all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands [1 July 2005-23 March 2016; n = 8049 IgM < 0·4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age-matched reference)]...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28976005/a-comparison-of-trecs-and-flow-cytometry-for-naive-t-cell-quantification
#19
S P Adams, S Kricke, E Ralph, N Gilmour, K C Gilmour
Assessment of thymic output by measurement of naive T cells is carried out routinely in clinical diagnostic laboratories, predominantly using flow cytometry with a suitable panel of antibodies. Naive T cell measurements can also be made using molecular analyses to quantify T cell receptor excision circle (TRECs) levels in sorted cells from peripheral blood. In this study we have compared TRECs levels retrospectively with CD45RA(+) CD27(+) T cells and also with CD45RA(+) CD31(+) T cells in 134 patient samples at diagnosis or during follow-up...
October 4, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28975999/combining-multiple-biomarkers-differentiates-between-active-sjia-sjia-mas-and-ebv-hlh
#20
L K Weaver
Cytokine storm syndromes are a clinically heterogeneous group of conditions resulting from a maladaptive host response to an inflammatory trigger. These syndromes lead to rapid progression of immune-mediated damage to healthy tissues resulting in life-threatening multi-system organ failure. Prompt recognition of disease and medical intervention to limit damage to healthy tissues is essential to prevent cytokine storm morbidity and mortality. However, the diagnosis of cytokine storm syndromes is challenging, given the clinical heterogeneity in disease presentations...
October 4, 2017: Clinical and Experimental Immunology
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