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Genes and Immunity

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https://www.readbyqxmd.com/read/27881839/a-polymorphism-in-human-mr1-is-associated-with-mrna-expression-and-susceptibility-to-tuberculosis
#1
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...
November 24, 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27829665/the-role-of-common-protective-alleles-hla-drb1-13-among-systemic-autoimmune-diseases
#2
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/27853145/marco-variants-are-associated-with-phagocytosis-pulmonary-tuberculosis-susceptibility-and-beijing-lineage
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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/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
#11
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
#12
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
https://www.readbyqxmd.com/read/27467285/survival-of-autoreactive-t-lymphocytes-by-microrna-mediated-regulation-of-apoptosis-through-trail-and-fas-in-type-1-diabetes
#13
V M de Jong, A R van der Slik, S Laban, R van 't Slot, B P C Koeleman, A Zaldumbide, B O Roep
Autoreactive CD8(+) T cells recognizing autoantigens expressed by pancreatic islets lead to the destruction of insulin-producing beta cells in type 1 diabetes (T1D), but these T cells also occur in healthy subjects. We tested the hypothesis that uncontrolled expansion of diabetogenic T cells in patients occurs, resulting from failure to activate apoptosis. We compared function, transcriptome and epigenetic regulation thereof in relation with fate upon repeated exposure to islet-autoantigen of islet autoreactive T cells from healthy and type 1 diabetic donors with identical islet epitope specificity and HLA-A2 restriction...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27467284/specific-hla-genotypes-confer-susceptibility-to-acute-necrotizing-encephalopathy
#14
A Hoshino, M Saitoh, T Miyagawa, M Kubota, J-I Takanashi, A Miyamoto, K Tokunaga, A Oka, M Mizuguchi
Acute necrotizing encephalopathy (ANE) is a rare and severe syndrome of acute encephalopathy triggered by viral infections. Cytokine storm is considered as the main pathogenetic mechanism of ANE. ANE is prevalent in East Asia, suggesting the association of host genetic factors. To elucidate the genetic background of Japanese ANE, we examined genotypes of human leukocyte antigen (HLA)-A, C, B, DRB1, DQB1 and DPB1 in 31 patients. Significant positive association was observed in both the allele frequency and positivity of DRB1*09:01 (P=0...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27467283/genetic-risk-and-longitudinal-disease-activity-in-systemic-lupus-erythematosus-using-targeted-maximum-likelihood-estimation
#15
M A Gianfrancesco, L Balzer, K E Taylor, L Trupin, J Nititham, M F Seldin, A W Singer, L A Criswell, L F Barcellos
Systemic lupus erythematous (SLE) is a chronic autoimmune disease associated with genetic and environmental risk factors. However, the extent to which genetic risk is causally associated with disease activity is unknown. We utilized longitudinal-targeted maximum likelihood estimation to estimate the causal association between a genetic risk score (GRS) comprising 41 established SLE variants and clinically important disease activity as measured by the validated Systemic Lupus Activity Questionnaire (SLAQ) in a multiethnic cohort of 942 individuals with SLE...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27467282/analysis-of-ly49-gene-transcripts-in-mature-nk-cells-supports-a-role-for-the-pro1-element-in-gene-activation-not-gene-expression
#16
M V McCullen, H Li, M Cam, S K Sen, D W McVicar, S K Anderson
The variegated expression of murine Ly49 loci has been associated with the probabilistic behavior of an upstream promoter active in immature cells, the Pro1 element. However, recent data suggest that Pro1 may be active in mature natural killer (NK) cells and function as an enhancer element. To assess directly if Pro1 transcripts are present in mature Ly49-expressing NK cells, RNA-sequencing of the total transcript pool was performed on freshly isolated splenic NK cells sorted for expression of either Ly49G or Ly49I...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27307212/ifnl3-4-genotype-is-associated-with-altered-immune-cell-populations-in-peripheral-blood-in-chronic-hepatitis-c-infection
#17
K S O'Connor, S A Read, M Wang, S Schibeci, M Eslam, A Ong, M D Weltman, M W Douglas, A Mazzola, A Craxì, S Petta, G J Stewart, C Liddle, J George, G Ahlenstiel, D R Booth
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27307211/reduction-of-gpsm3-expression-akin-to-the-arthritis-protective-snp-rs204989-differentially-affects-migration-in-a-neutrophil-model
#18
B J Gall, A B Schroer, J D Gross, V Setola, D P Siderovski
G Protein Signaling Modulator-3 (GPSM3) is a leukocyte-specific regulator of G protein-coupled receptors (GPCRs), which binds inactivated Gαi·GDP subunits and precludes their reassociation with Gβγ subunits. GPSM3 deficiency protects mice from inflammatory arthritis and, in humans, GPSM3 single-nucleotide polymorphisms (SNPs) are inversely associated with the risk of rheumatoid arthritis development; recently, these polymorphisms were linked to one particular SNP (rs204989) that decreases GPSM3 transcript abundance...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27278128/phorbol-ester-mediated-re-expression-of-endogenous-lat-adapter-in-j-cam2-cells-a-model-for-dissecting-drivers-and-blockers-of-lat-transcription
#19
K Marek-Bukowiec, E Aguado, A Miazek
Linker for activation of T cells (LAT) is a raft-associated, transmembrane adapter protein critical for T-cell development and function. LAT expression is transiently upregulated upon T-cell receptor (TCR) engagement, but molecular mechanisms conveying TCR signaling to enhanced LAT transcription are not fully understood. Here we found that a Jurkat subline J.CaM2, initially characterized as LAT deficient, conditionally re-expressed LAT upon the treatment with a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA)...
July 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27278127/gene-disease-association-with-human-ifnl-locus-polymorphisms-extends-beyond-hepatitis-c-virus-infections
#20
REVIEW
S Chinnaswamy
Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus...
July 2016: Genes and Immunity
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