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Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
Wenjie Zhao, Xiaoyang Yue, Kuai Liu, Junfeng Zheng, Runda Huang, Jun Zou, Gabriela Riemekasten, Frank Petersen, Xinhua Yu
Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF(+)-SSc and PF(-)-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc...
April 22, 2017: Rheumatology International
Paraskevi Chairta, Paschalis Nicolaou, Kyproula Christodoulou
Systemic sclerosis is an autoimmune rheumatic disease characterised by fibrosis, vasculopathy and inflammation. The exact aetiology of SSc remains unknown but evidences show that various genetic factors may be involved. This review aimed to assess HLA alleles/non-HLA polymorphisms, microsatellites and chromosomal abnormalities that have thus far been associated with SSc. PubMed, Embase and Scopus databases were searched up to July 29, 2015 using a combination of search-terms. Articles retrieved were evaluated based on set exclusion and inclusion criteria...
February 2017: Human Immunology
Dan Holmberg, Karin Ruikka, Petter Lindgren, Mats Eliasson, Sofia Mayans
BACKGROUND: T1D and AITD are autoimmune disorders commonly occurring in the same family and even in the same individual. The genetic contribution to these disorders is complex making uncovering of susceptibility genes very challenging. The general aim of this study was to identify loci and genes contributing to T1D/AITD susceptibility. Our strategy was to perform linkage and association studies in the relatively genetically homogenous population of northern Sweden. We performed a GWLS to find genomic regions linked to T1D/AITD in families from northern Sweden and we performed an association study in the families to test for association between T1D/AITD and variants in previously published candidate genes as well as a novel candidate gene, CD247...
October 4, 2016: BMC Medical Genetics
Ana V Marin, Anaïs Jiménez-Reinoso, Alejandro C Briones, Miguel Muñoz-Ruiz, Cigdem Aydogmus, Luke J Pasick, Jorge Couso, Marina S Mazariegos, Angel F Alvarez-Prado, Alfonso Blázquez-Moreno, Funda E Cipe, Sule Haskologlu, Figen Dogu, Matías Morín, Miguel A Moreno-Pelayo, Félix García-Sánchez, Juana Gil-Herrera, Edgar Fernández-Malavé, Hugh T Reyburn, Almudena R Ramiro, Aydan Ikinciogullari, Maria J Recio, Jose R Regueiro, Beatriz Garcillán
No abstract text is available yet for this article.
August 20, 2016: Journal of Allergy and Clinical Immunology
Yoshihiro Inamoto, Paul J Martin, Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Edus H Warren, Daniel E Geraghty, Ni Lee, Michael J Boeckh, Barry E Storer, David M Levine, Wenhong Fan, Lue-Ping Zhao, John A Hansen
Sclerotic graft-versus-host disease (GVHD) is a distinctive phenotype of chronic GVHD after allogeneic hematopoietic cell transplantation, characterized by fibrosis of skin or fascia. Sclerotic GVHD has clinical and histopathological similarities with systemic sclerosis, an autoimmune disease whose risk is influenced by genetic polymorphisms. We examined 13 candidate single-nucleotide polymorphisms (SNPs) that have a well-documented association with systemic sclerosis to determine whether these SNPs are also associated with the risk of sclerotic GVHD...
September 15, 2016: Blood
Moshe Sade-Feldman, Julia Kanterman, Yair Klieger, Eliran Ish-Shalom, Mizrahi Olga, Amijai Saragovi, Hani Shtainberg, Michal Lotem, Michal Baniyash
PURPOSE: High levels of circulating myeloid-derived suppressor cells (MDSCs) in various cancer types, including melanoma, were shown to correlate with poor survival. We investigated whether frequencies of circulating CD33(+)CD11b(+)HLA-DR(-) MDSCs could be used as immune system monitoring biomarkers to predict response and survival of patients with stage IV melanoma treated with anti-CTLA4 (ipilimumab) therapy. EXPERIMENTAL DESIGN: Peripheral blood samples from 56 patients and 50 healthy donors (HDs) were analyzed for CD33(+)CD11b(+)HLA-DR(-) MDSC percentage, NO(-), and hROS levels by flow cytometry...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
F David Carmona, Ahmet Mesut Onat, Tamara Fernández-Aranguren, Alberto Serrano-Fernández, Gema Robledo, Haner Direskeneli, Amr H Sawalha, Sule Yavuz, Javier Martín
OBJECTIVE: To evaluate the genetic background of systemic sclerosis (SSc) in the Turkish population. METHODS: There were 354 cases and 718 unaffected controls from Turkey genotyped for the most relevant SSc genetic markers (IRF5-rs10488631, STAT4-rs3821236, CD247-rs2056626, DNASE1L3-rs35677470, IL12A-rs77583790, and ATG5-rs9373839). Association tests were conducted to identify possible associations. RESULTS: Except for ATG5, all the analyzed genes showed either significant associations (IRF5: p = 1...
July 2016: Journal of Rheumatology
Peng Li, Xiu Wang, Meng-Qin Zhao, Lian-Ju Li, Chao Zhang, Bao-Zhu Li, Juan Liu, Xiao-Ke Yang, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
OBJECTIVES: Recent evidence has demonstrated that CD3ζ (also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and health controls. METHODS: Three CD247 polymorphisms (rs704853, rs1214611 and rs858554) were studied in 612 patients with RA and 848 controls in a Chinese population...
April 26, 2016: Autoimmunity
Cielito C Reyes-Gibby, Jian Wang, Mary Rose T Silvas, Robert Yu, Sai-Ching J Yeung, Sanjay Shete
BACKGROUND: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search...
February 13, 2016: BMC Genetics
Colleen A Mangold, Dustin R Masser, David R Stanford, Georgina V Bixler, Aditya Pisupati, Cory B Giles, Jonathan D Wren, Matthew M Ford, William E Sonntag, Willard M Freeman
The major histocompatibility complex I (MHCI) pathway, which canonically functions in innate immune viral antigen presentation and detection, is functionally pleiotropic in the central nervous system (CNS). Alternative roles include developmental synapse pruning, regulation of synaptic plasticity, and inhibition of neuronal insulin signaling; all processes altered during brain aging. Upregulation of MHCI components with aging has been reported; however, no systematic examination of MHCI cellular localization, expression, and regulation across CNS regions, life span, and sexes has been reported...
January 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Eliran Ish-Shalom, Yaron Meirow, Moshe Sade-Feldman, Julia Kanterman, Lynn Wang, Olga Mizrahi, Yair Klieger, Michal Baniyash
Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition...
January 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Thais A Fornari, Paula B Donate, Amanda F Assis, Claudia Macedo, Elza T Sakamoto-Hojo, Eduardo A Donadi, Geraldo A Passos
In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown...
2015: PloS One
Mar Valés-Gómez, Gloria Esteso, Cigdem Aydogmus, Alfonso Blázquez-Moreno, Ana V Marín, Alejandro C Briones, Beatriz Garcillán, Eva-María García-Cuesta, Sheila López Cobo, Sule Haskologlu, Manuela Moraru, Funda Cipe, Kerry Dobbs, Figen Dogu, Silvia Parolini, Luigi D Notarangelo, Carlos Vilches, Maria J Recio, José R Regueiro, Aydan Ikinciogullari, Hugh T Reyburn
No abstract text is available yet for this article.
March 2016: Journal of Allergy and Clinical Immunology
Maia Limbach, Mario Saare, Liina Tserel, Kai Kisand, Triin Eglit, Sascha Sauer, Tomas Axelsson, Ann-Christine Syvänen, Andres Metspalu, Lili Milani, Pärt Peterson
In Graves' disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively...
February 2016: Journal of Autoimmunity
Eva Krepsova, Irena Tycova, Alena Sekerkova, Peter Wohlfahrt, Petra Hruba, Ilja Striz, Birgit Sawitzki, Ondrej Viklicky
BACKGROUND: Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects. METHODS: The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx...
August 19, 2015: BMC Nephrology
D Wang, F Cai, J Ge, L Yin
We aimed to give a systematic hypothesis on the functions of exercise on circulating monocytes by identifying a discrete set of genes in circulating monocytes that were altered by exercise. The microarray expression profile of GSE51835 was downloaded from gene expression omnibus (GEO) database for the identification of differentially expressed genes (DEGs) using limma and affy packages in R language. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for DEGs, followed by the construction of co-expression network and protein-protein interaction (PPI) network...
November 2015: Scandinavian Journal of Immunology
Zhicai Shi, Quan Li, Bin Cai, Bo Ran, Ming Li
STUDY DESIGN: A comprehensive bioinformatics analysis of genes which may have correlations with ankylosing spondylitis (AS). OBJECTIVE: To study the mechanisms of AS by analyzing microarray of GSE25101. SUMMARY OF BACKGROUND DATA: AS is an inflammatory arthritis that can lead to chronic pain and disability. MATERIALS AND METHODS: GSE25101 was downloaded from Gene Expression Omnibus including 16 AS patients and 16 normal controls...
May 2015: Journal of Spinal Disorders & Techniques
Petros Christopoulos, Elaine P Dopfer, Miroslav Malkovsky, Philipp R Esser, Hans-Eckart Schaefer, Alexander Marx, Sylvia Kock, Nicole Rupp, Myriam R Lorenz, Klaus Schwarz, Jan Harder, Stefan F Martin, Martin Werner, Christian Bogdan, Wolfgang W A Schamel, Paul Fisch
The mechanisms underlying thymoma-associated immunodeficiency are largely unknown, and the significance of increased blood γδ Τ cells often remains elusive. In this study we address these questions based on an index patient with thymoma, chronic visceral leishmaniasis, myasthenia gravis, and a marked increase of rare γδ T cell subsets in the peripheral blood. This patient showed cutaneous anergy, even though he had normal numbers of peripheral blood total lymphocytes as well as CD4(+) and CD8(+) T cells...
April 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Jing Song, Yue Li, Rui Fang An
BACKGROUND: Early-onset preeclampsia (EOPET), resulting in intrauterine growth restriction, has serious impact on maternal, perinatal, and neonatal livability worldwide. The current study conducted bioinformatics analyses to screen key genes and microRNAs (miRNAs) involved in EOPET and thus to explore the molecular mechanisms of EOPET. METHODS: The microarray data set GSE44711 containing 8 EOPET placentas and 8 gestational age-matched controls was obtained from the Gene Expression Omnibus database...
August 2015: Reproductive Sciences
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