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Genes and Immunity

Hongwei Li, Guochao Wang, Huanhu Zhang, Xin Song, Jianzhong Cao, Xiaqin Zhang, Ruiqi Xue, Weili Wang, Sufang Jia, Zhengran Li
The prognostic value of the systemic immune-inflammation index (SII) has been shown in various types of cancers. We aimed to evaluate the predictive values in brain metastases from lung adenocarcinoma with status of EGFR mutations. We, retrospectively, examined 310 patients with brain metastases from lung adenocarcinoma with status of EGFR mutations. SII was calculated using P * N/L, where P, N, and L, respectively refer to peripheral blood lymphocyte, neutrophil, and platelet counts. The cut-off value of SII was assessed by area under the curve (AUC)...
November 9, 2018: Genes and Immunity
Christian Lundtoft, Anthony Afum-Adjei Awuah, Alptekin Güler, Kirstin Harling, Heiner Schaal, Ertan Mayatepek, Richard O Phillips, Norman Nausch, Ellis Owusu-Dabo, Marc Jacobsen
Functional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants. Six exonic IL7RA polymorphisms were genotyped and two minor alleles were found at lower frequencies in tuberculosis patients as compared to healthy contacts from Ghana (rs11567764, p = 0...
October 31, 2018: Genes and Immunity
Giuseppe Raschellà, Gerry Melino, Alessandra Gambacurta
Tumors constitute a large class of diseases that affect different organs and cell lineages. The molecular characterization of cancers of a given type has revealed an extraordinary heterogeneity in terms of genetic alterations and DNA mutations; heterogeneity that is further highlighted by single-cell DNA sequencing of individual patients. To address these issues, drugs that specifically target genes or altered pathways in cancer cells are continuously developed. Indeed, the genetic fingerprint of individual tumors can direct the modern therapeutic approaches to selectively hit the tumor cells while sparing the healthy ones...
October 19, 2018: Genes and Immunity
Paola Giglio, Mara Gagliardi, Roberta Bernardini, Maurizio Mattei, Diego Cotella, Claudio Santoro, Mauro Piacentini, Marco Corazzari
Skin melanoma remains one of the most aggressive and difficult to treat human malignancy, with an increasing incidence every year. Although surgical resection represents the best therapeutic approach, this is only feasible in cases of early diagnosis. Furthermore, the established malignancy is resistant to all therapeutic strategies employed so far, resulting in an unacceptable patient survival rate. Although the immune-mediated therapeutic approaches, based on anti-PD1 or anti-CTLA4, are very promising and under clinical trial experimentation, they could conceal not yet fully emerged pitfalls such as the development of autoimmune diseases...
October 4, 2018: Genes and Immunity
Jun-Min Lu, Yuan-Cheng Chen, Zeng-Xin Ao, Jie Shen, Chun-Ping Zeng, Xu Lin, Lin-Ping Peng, Rou Zhou, Xia-Fang Wang, Cheng Peng, Hong-Mei Xiao, Kun Zhang, Hong-Wen Deng
Genome-wide association studies (GWASs) have discovered >50 risk loci for type 1 diabetes (T1D). However, those variations only have modest effects on the genetic risk of T1D. In recent years, accumulated studies have suggested that gene-gene interactions might explain part of the missing heritability. The purpose of our research was to identify potential and novel risk genes for T1D by systematically considering the gene-gene interactions through network analyses. We carried out a novel system network analysis of summary GWAS statistics jointly with transcriptomic gene expression data to identify some of the missing heritability for T1D using weighted gene co-expression network analysis (WGCNA)...
September 24, 2018: Genes and Immunity
Bing Liu, Lisa A Maier, Nabeel Hamzeh, Kristyn MacPhail, Margaret M Mroz, Hongbo Liu, Li Li
Previously we showed that alveolar macrophages (AMs) from patients with chronic beryllium disease (CBD) and beryllium sensitization (BeS) demonstrated significantly greater cell surface CD16 (encoded by the FCGR3A gene) than controls. We hypothesized that these differences were related to polymorphisms in the FCGR3A gene. This study was to determine the association between FCGR3A polymorphisms in CBD, BeS versus controls as well as clinical data, providing potential information about disease pathogenesis, risk, and activity...
September 24, 2018: Genes and Immunity
Brigitte Glanzmann, Caitlin Uren, Nikola de Villiers, Ansia van Coller, Richard H Glashoff, Michael Urban, Eileen G Hoal, Monika M Esser, Marlo Möller, Craig J Kinnear
While individual primary immunodeficiency diseases (PIDs) are rare, collectively they represent a significant burden of disease. Recent estimates show that about one million people in Africa suffer from a PID. However, data from African PID registries reflect only a small percentage of the estimated prevalence. This disparity is partly due to the lack of PID awareness and the masking of PIDs by the endemic pathogens. Over three million tuberculosis (TB) cases were reported in Africa in 2016, with many of these from southern Africa...
September 6, 2018: Genes and Immunity
Marie Fechtenbaum, Judith Desoutter, Gauthier Delvallez, Etienne Brochot, Nicolas Guillaume, Vincent Goëb
The major histocompatibility complex class I polypeptide-related sequence A (MICA) glycoprotein mediates the activation of the natural killer group 2D receptor (NKG2D) expressed on NK and CD8+ T cells. A methionine or valine at position 129 in exon 3 results in strong (MICA129 met) or weak (MICA129 val) binding to NKG2D. The MICA A5.1 allele causes a premature stop codon. Various NKG2D polymorphisms are associated with low (NKC3 C/C and NKC4 C/C) or high (NKC3 G/G and NKC4 T/T) levels of NK cell cytotoxic activity...
September 4, 2018: Genes and Immunity
Ming-Liang Zhang, Dong-Ming Zhang, Cai-E Wang, Xiao-Long Chen, Fang-Zhou Liu, Jian-Xue Yang
Emerging evidence revealed that thyroglobulin (TG) contributes to the development of autoimmune disease, and the relationship between TG and autoimmune thyroid disease (AITD) is still controversial. The aim of this study was to quantify the association between rs2076740, rs853326, rs180223, and rs2069550 TG polymorphisms and risk of AITD using a meta-analysis approach. We identified all studies that assessed the association between TG polymorphisms and AITD from PubMed, Embase, and Web of Science databases...
August 24, 2018: Genes and Immunity
Thomas Brunner, Marie-Lise Gougeon
No abstract text is available yet for this article.
August 17, 2018: Genes and Immunity
Robert P Igo, Noémi B Hall, LaShaunda L Malone, Jacob B Hall, Barbara Truitt, Feiyou Qiu, Li Tao, Ezekiel Mupere, Audrey Schnell, Thomas R Hawn, William S Bush, Moses Joloba, W Henry Boom, Catherine M Stein
Tuberculosis (TB) is a major public health burden worldwide, and more effective treatment is sorely needed. Consequently, uncovering causes of resistance to Mycobacterium tuberculosis (Mtb) infection is of special importance for vaccine design. Resistance to Mtb infection can be defined by a persistently negative tuberculin skin test (PTST-) despite living in close and sustained exposure to an active TB case. While susceptibility to Mtb is, in part, genetically determined, relatively little work has been done to uncover genetic factors underlying resistance to Mtb infection...
August 13, 2018: Genes and Immunity
Ying Zhou, Jun Wu, Wei Wang, Mingfang Sun
The original version of this article omitted the corresponding author Mingfang Sun and the author Ying Zhou from the Division of Rheumatology, Research Institute of Surgery, Daping Hospital, the Army Medical University, Chongqing 400042, China. This has now been corrected in the PDF and HTML versions of the article.
July 9, 2018: Genes and Immunity
Kate F Kernan, Lina Ghaloul-Gonzalez, Bita Shakoory, John A Kellum, Derek C Angus, Joseph A Carcillo
Post-hoc subgroup analysis of the negative trial of interleukin-1β receptor antagonist (IL1RA) for septic shock suggested that patients with features of macrophage activation syndrome (MAS) experienced a 50% relative risk reduction for mortality with treatment. Here we seek a genetic basis for this differential response. From 1341 patients enrolled in the ProCESS trial of early goal directed therapy for septic shock, we selected 6 patients with MAS features and the highest ferritin, for whole exome sequencing (mean 24,030...
July 6, 2018: Genes and Immunity
Michelle M Stein, Cara L Hrusch, Anne I Sperling, Carole Ober
The low affinity Fcγ receptor, FcγRIIA, harbors a common missense mutation, rs1801274 (G>A, Arg131His) that modifies binding affinity to human IgG2 and mouse IgG1 antibodies and is associated with increased risk of autoimmune disease. Despite the important role of the Arg131His variant, little is understood about heterozygous genotype effects on global gene expression and cytokine production during an FcγR-dependent response. To address this gap in knowledge, we treated human whole-blood samples from 130 individuals with mouse IgG1 anti-CD3 and anti-CD28 antibodies and characterized the genome-wide gene expression profiles and cytokine production among individuals stratified by rs1801274 genotype...
July 6, 2018: Genes and Immunity
Yan Teng, Mingqi Luo, Ting Yu, Lang Chen, Qiuling Huang, Shuliang Chen, Linlin Xie, Yan Zeng, Fan Luo, Hairong Xiong, Yuanyuan Liu, Wei Hou, Yong Feng
The human immunodeficiency virus type 1 (HIV-1) causes persistent infection in human and induces miR-146a expression in infected cells. miR-146a represses the innate immune response by inhibiting the expression of TRAF6 and IRAK1 genes, thus negatively controls the NF-κB-related cytokines and interferon stimulated genes. Here we reported that lentiviral CRISPR/Cas9 system was highly efficient in introducing mutations in the precursor miR-146a genomic sequences, resulting in a loss of miR-146a expression and function...
July 2, 2018: Genes and Immunity
Peter S Linsley, Carla J Greenbaum, Mario Rosasco, Scott Presnell, Kevan C Herold, Matthew J Dufort
Biologic treatment of type 1 diabetes (T1D) with agents including anti-CD3 (otelixizumab and teplizumab), anti-CD20 (rituximab), LFA3Ig (alafacept), and CTLA4Ig (abatacept) results in transient stabilization of insulin C-peptide, a surrogate for endogenous insulin secretion. With the goal of inducing more robust immune tolerance, we used systems biology approaches to elucidate mechanisms associated with C-peptide stabilization in clinical trial blood samples from new-onset T1D subjects treated with the B cell-depleting drug, rituximab...
June 21, 2018: Genes and Immunity
Jing Xu, Yan Shang, Feng Cai, Shu Zhang, Zhong Xiao, Haitao Wang, Yanhong Fan, Ting Li, Shuhong Sheng, Youhui Fu, Feng Chi, Chen Zhou
To further investigate the relationship between lung cancer and hedgehog interacting protein (HHIP) polymorphisms of chronic obstructive pulmonary disease (COPD) patients, we conducted a case-control study in a Chinese Han population. Six HHIP SNPs with minor allele frequencies >5% (rs1489758, rs1489759, rs10519717, rs13131837, rs1492820, and rs7689420) were analyzed in 1,017 COPD patients (767 males and 246 females) and 430 non-COPD patients. Using logistic regression analysis, we found that rs7689420 was significantly associated with lung cancer in COPD patients in the Chinese Han population (P < 0...
June 19, 2018: Genes and Immunity
Steven J Mack, Julia Udell, Franziska Cohen, Kazutoyo Osoegawa, Sharon K Hawbecker, David A Noonan, Martha B Ladner, Damian Goodridge, Elizabeth A Trachtenberg, Jorge R Oksenberg, Henry A Erlich
Since the publication of this article, the authors have found that the numbers of patients and controls were reversed. This study included 412 MS patients and 419 controls. This correction applies to the Abstract, the final paragraph of the Introduction, and the first paragraph of the Materials and Methods. This was entirely a reporting error and does not impact the Results or Conclusions.
June 18, 2018: Genes and Immunity
Nicolas De Neuter, Esther Bartholomeus, George Elias, Nina Keersmaekers, Arvid Suls, Hilde Jansens, Evelien Smits, Niel Hens, Philippe Beutels, Pierre Van Damme, Geert Mortier, Viggo Van Tendeloo, Kris Laukens, Pieter Meysman, Benson Ogunjimi
Pathogens of past and current infections have been identified directly by means of PCR or indirectly by measuring a specific immune response (e.g., antibody titration). Using a novel approach, Emerson and colleagues showed that the cytomegalovirus serostatus can also be accurately determined by using a T cell receptor repertoire data mining approach. In this study, we have sequenced the CD4+ memory T cell receptor repertoire of a Belgian cohort with known cytomegalovirus serostatus. A random forest classifier was trained on the CMV specific T cell receptor repertoire signature and used to classify individuals in the Belgian cohort...
June 15, 2018: Genes and Immunity
Leah C Kottyan, Avery Maddox, Julian R Braxton, Emily M Stucke, Vince Mukkada, Philip E Putnam, J Pablo Abonia, Mirna Chehade, Robert A Wood, Robbie D Pesek, Brian P Vickery, Glenn T Furuta, Peter Dawson, Hugh A Sampson, Lisa J Martin, Jennifer A Kelly, Robert P Kimberly, Kathy Sivils, Patrick M Gaffney, Kenneth Kaufman, John B Harley, Marc E Rothenberg
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS...
June 8, 2018: Genes and Immunity
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