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Genes and Immunity

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https://www.readbyqxmd.com/read/28123183/epistatic-effect-of-tlr-1-6-and-10-polymorphisms-on-organic-dust-mediated-cytokine-response
#1
L M Smith, L A Weissenburger-Moser, A J Heires, K L Bailey, D J Romberger, T D LeVan
Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan...
January 26, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28077880/interleukin-2-receptor-%C3%AE-proximal-promoter-hypomethylation-is-associated-with-multiple-sclerosis
#2
J Field, A Fox, M A Jordan, A G Baxter, T Spelman, M Gresle, H Butzkueven, T J Kilpatrick, J P Rubio
Genetic studies have demonstrated association between single-nucleotide polymorphisms within the IL2RA (interleukin-2 receptor α-subunit) gene and risk of developing multiple sclerosis (MS); however, these variants do not have obvious functional consequences. DNA methylation is a source of genetic variation that could impact on autoimmune disease risk. We investigated DNA methylation of the IL2RA promoter in genomic DNA obtained from peripheral blood mononuclear cells and neural tissue using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry...
January 12, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28053322/vav1-regulates-experimental-autoimmune-arthritis-and-is-associated-with-anti-ccp-negative-rheumatoid-arthritis
#3
A O Guerreiro-Cacais, U Norin, A Gyllenberg, R Berglund, A D Beyeen, E Petit-Teixeira, F Cornélis, A Saoudi, G J Fournié, R Holmdahl, L Alfredsson, L Klareskog, M Jagodic, T Olsson, I Kockum, L Padyukov
Rheumatoid arthritis (RA) patients can be stratified into two subgroups defined by the presence or absence of antibodies against citrullinated circular peptides (anti-CCP) with most of the genetic association found in anti-CCP positive RA. Here we addressed the role of VAV1, previously associated to multiple sclerosis (MS), in the pathogenesis of RA in experimental models and in a genetic association study. Experimental arthritis triggered by pristane or collagen type II was induced in DA rats and in the DA...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28053321/functionality-and-opposite-roles-of-two-interleukin-4-haplotypes-in-immune-cells
#4
G Anovazzi, M C Medeiros, S C Pigossi, L S Finoti, T M Souza Moreira, M P A Mayer, C F Zanelli, S R Valentini, C Rossa-Junior, R M Scarel-Caminaga
Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCI/CCI haplotype (Hap-2) in the IL4 gene formed by the -590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these IL4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with Ionomycin and IL-1β (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28053320/direct-measurement-of-b-cell-receptor-repertoire-s-composition-and-variation-in-systemic-lupus-erythematosus
#5
S Liu, X L Hou, W G Sui, Q J Lu, Y L Hu, Y Dai
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyper-reactivity. B-cell receptor (BCR) has a central role in B-cell development, activation, survival and apoptosis, and thus is a critical component of the regulation of both protective and autoreactive B cells. In this study, we applied multiplex PCR and Illumina high-throughput sequencing to study the composition and variation of the BCRs in peripheral blood mononuclear cells from SLE patients and healthy donors (NC)...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28053319/pre-diagnostic-genotyping-identifies-t1d-subjects-with-impaired-treg-il-2-signaling-and-an-elevated-proportion-of-foxp3-il-17-cells
#6
A K Marwaha, C Panagiotopoulos, C M Biggs, S Staiger, K L Del Bel, A F Hirschfeld, J J Priatel, S E Turvey, R Tan
T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3(lo) Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28031553/genetic-origin-of-beh%C3%A3-et-s-disease-population-in-denizli-turkey-population-genetics-data-analysis-historical-demography-and-geographical-perspectives-based-on-%C3%AE-globin-gene-cluster-haplotype-variation
#7
O Ozturk, S Arikan, A Bahadir, A Atalay, E O Atalay
In our study, we aimed to investigate the possible genetic drift, relationships, expansion and historical origin based on haplotype frequencies of the β-globin gene cluster of normal and Behçet's disease (BD) population in Denizli, Turkey. We examined blood DNA samples obtained from our DNA bank. The association of population genetic parameters such as haplotypes, diversity, differentiation, Hardy-Weinberg equilibrium and demographic analysis for two populations was performed by Arlequin ver. 3.5. Our results show that both populations have high similarity in genetic parameters in terms of development and expansion based on haplotype diversity through the history...
December 29, 2016: Genes and Immunity
https://www.readbyqxmd.com/read/28031552/autophagy-related-irgm-genes-confer-susceptibility-to-ankylosing-spondylitis-in-a-chinese-female-population-a-case-control-study
#8
Q Xia, M Wang, X Yang, X Li, X Zhang, S Xu, Z Shuai, J Xu, D Fan, C Ding, F Pan
It is known that ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) shared a common genetic component. The gist of current study is to assess the role of IBD-associated autophagy gene IRGM on AS susceptibility in a Chinese Han population. A total of 1270 unrelated subjects (643 AS and 627 controls) were enrolled. Two tag single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958846) were selected and were genotyped by iMLDR Assay technology. Genotypes and haplotype analysis were conducted by using SPSS 16...
December 29, 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27881839/a-polymorphism-in-human-mr1-is-associated-with-mrna-expression-and-susceptibility-to-tuberculosis
#9
C Seshadri, N T T Thuong, N T H Mai, N D Bang, T T H Chau, D M Lewinsohn, G E Thwaites, S J Dunstan, T R Hawn
The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis...
January 2017: Genes and Immunity
https://www.readbyqxmd.com/read/27853145/marco-variants-are-associated-with-phagocytosis-pulmonary-tuberculosis-susceptibility-and-beijing-lineage
#10
N T T Thuong, T T B Tram, T D Dinh, P V K Thai, D Heemskerk, N D Bang, T T H Chau, D G Russell, G E Thwaites, T R Hawn, M Caws, S J Dunstan
Macrophage receptor with collagenous structure (MARCO) has an important role in the phagocytosis of Mycobacterium tuberculosis (M. tuberculosis). We hypothesized that MARCO polymorphisms are associated with phagocytosis, tuberculosis (TB) disease susceptibility and presentation, and infecting lineage. We used a human cellular model to examine how MARCO genotype mediates the immune response; a case-control study to investigate tuberculosis host genetic susceptibility; and a host-pathogen genetic analysis to study host-pathogen interactions...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27853144/hla-class-i-and-ii-alleles-heterozygosity-and-hla-kir-interactions-are-associated-with-rates-of-genital-hsv-shedding-and-lesions
#11
A Magaret, L Dong, M John, S A Mallal, I James, T Warren, S Gaudieri, D M Koelle, A Wald
Variation at HLA and KIR loci is associated with the severity of viral infections. To assess associations of genital HSV-2 infection with human HLA and KIR genetic loci, we measured the frequencies of genital herpes simplex virus (HSV) DNA detection and of genital lesions in HSV-2 seropositive persons. We followed 267 HSV-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days. All persons were laboratory-documented as HIV-seronegative, and all were Caucasian by self-report...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27829666/autoimmune-risk-variants-in-erap2-are-associated-with-gene-expression-levels-in-thymus
#12
I S M Gabrielsen, M K Viken, S S Amundsen, H Helgeland, K Holm, S T Flåm, B A Lie
Genetic polymorphisms in the endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 genes have been associated with several autoimmune diseases (AIDs) at a genome-wide significance level. In this study, we performed a cis expression quantitative trait locus (eQTL) screen to investigate whether seven fine-mapped AID single-nucleotide polymorphisms (SNPs) in the ERAP-region influence the gene-expression levels of ERAP1 and ERAP2 in thymus. After quality control, we identified six significant eQTLs. We further assessed the peak eQTL signals, and both genes showed highly significant and independent thymic eQTL signals (P=2...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27786174/fecal-metabolomics-in-pediatric-spondyloarthritis-implicate-decreased-metabolic-diversity-and-altered-tryptophan-metabolism-as-pathogenic-factors
#13
M L Stoll, R Kumar, E J Lefkowitz, R Q Cron, C D Morrow, S Barnes
We have previously shown alterations in the composition of the gut microbiota in children with enthesitis-related arthritis (ERA). To explore the mechanisms by which an altered microbiota might predispose to arthritis, we performed metabolomic profiling of fecal samples of children with ERA. Fecal samples were collected from two cohorts of children with ERA and healthy control subjects. Nano-liquid chromatography-mass spectroscopy (LC-MS) was performed on the fecal water homogenates with identification based upon mass: charge ratios...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27708262/evaluation-of-kir3dl1-kir3ds1-polymorphism-in-beh%C3%A3-et-s-disease
#14
B Erer, M Takeuchi, D Ustek, I Tugal-Tutkun, E Seyahi, Y Özyazgan, J Duymaz-Tozkir, A Gül, D L Kastner, E F Remmers, M J Ombrello
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27653816/natural-genetic-variation-profoundly-regulates-gene-expression-in-immune-cells-and-dictates-susceptibility-to-cns-autoimmunity
#15
F Bearoff, R Del Rio, L K Case, J A Dragon, T Nguyen-Vu, C-Y Lin, E P Blankenhorn, C Teuscher, D N Krementsov
Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naive immune cell types relevant to MS...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27581100/maternal-and-child-cytokine-relationship-in-early-life-is-not-altered-by-cytokine-gene-polymorphisms
#16
Y Djuardi, T Supali, H Wibowo, B T Heijmans, J Deelen, E P Slagboom, J J Houwing-Duistermaat, E Sartono, M Yazdanbakhsh
The development of immune responses is influenced by the interaction between environmental and genetic factors. Our previous study showed a close association between maternal and young infant's cytokine responses. The question is how this association evolves over time and the contribution of genetic polymorphisms to this association. Five cytokines in mitogen-stimulated whole blood culture were measured from pregnant mothers and their children aged 2, 5, 12, 24 and 48 months. Cytokine gene polymorphisms were determined in both mothers and children...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27534615/gene-signatures-associated-with-adaptive-humoral-immunity-following-seasonal-influenza-a-h1n1-vaccination
#17
I G Ovsyannikova, H M Salk, R B Kennedy, I H Haralambieva, M T Zimmermann, D E Grill, A L Oberg, G A Poland
This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27829665/the-role-of-common-protective-alleles-hla-drb1-13-among-systemic-autoimmune-diseases
#18
REVIEW
H Furukawa, S Oka, N Tsuchiya, K Shimada, A Hashimoto, S Tohma, A Kawasaki
Associations between human leukocyte antigen (HLA) and susceptibility to systemic autoimmune diseases have been reported. The predisposing alleles are variable among ethnic groups and/or diseases. On the other hand, some HLA alleles are associated with resistance to systemic autoimmune diseases, including systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Interestingly, DRB1*13 alleles are the protective alleles shared by multiple autoimmune diseases. DRB1*13:01 allele is protective in European populations and DRB1*13:02 in Japanese...
November 10, 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27467287/cd58-mutations-are-common-in-hodgkin-lymphoma-cell-lines-and-loss-of-cd58-expression-in-tumor-cells-occurs-in-hodgkin-lymphoma-patients-who-relapse
#19
F R Abdul Razak, A Diepstra, L Visser, A van den Berg
CD58 is involved in immune recognition of tumor cells via binding of the CD2 receptor expressed on cytotoxic T cells. In diffuse large B-cell lymphoma, mutations of the CD58 gene are reported to contribute to immune evasion of the tumor cells. We previously showed CD58 mutations in three Hodgkin lymphoma (HL) cell lines by whole-exome sequencing. In this study, we confirmed the mutations by Sanger sequencing at the DNA and RNA level and showed low levels or total loss of CD58 mRNA expression in two of the three cell lines...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27467286/dual-effects-of-testosterone-in-behcet-s-disease-implications-for-a-role-in-disease-pathogenesis
#20
S Yavuz, T Akdeniz, V Hancer, M Bicakcigil, M Can, G Yanikkaya-Demirel
Behcet's disease (BD) exhibits more severe disease course and higher mortality among male patients. However, underlying mechanisms of gender differences in clinical manifestations and disease severity are unclear. The aim of this study was to determine whether testosterone (T) has any role on BD pathogenesis. We studied peripheral blood mononuclear cells (PBMC) and neutrophils of BD patients and controls. Functional assay of neutrophils, cytokine measurements of culture supernatants and gene expressions on both cells were analyzed before and after T incubation...
September 2016: Genes and Immunity
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