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Genes and Immunity

Jun Wu, Wei Wang
The present study was aimed at identifying the association between interleukin family gene polymorphisms and recurrent aphthous stomatitis (RAS) risk using a meta-analysis. We searched the PubMed, web of science, Embase and ScienceDirect-Elsevier databases for research on the interleukin polymorphism and RAS risk. In total 12 studies were included to investigate the relationships between RAS risk and six polymorphisms by calculating pooled odds ratios (ORs) and 95% confidence intervals (CIs). A significant association was found between IL-1β+3954C/T polymorphism and RAS risk...
March 18, 2018: Genes and Immunity
Kozue Uchio-Yamada, Mayuri Tanaka, Noboru Manabe
C1s deficiency is strongly associated with the development of human systemic lupus erythematosus (SLE); however, the mechanisms by which C1s deficiency contributes to the development of SLE have not yet been elucidated in detail. Using ICR-derived-glomerulonephritis (ICGN) mouse strain that develops SLE and very weakly expresses C1s in the liver, we investigated the protective roles of C1s against SLE. A genetic sequence analysis revealed complete deletion of the C1s1 gene, a mouse homolog of the human C1s gene, with partial deletion of the C1ra and C1rb genes in the ICGN strain...
March 18, 2018: Genes and Immunity
Asher Haug-Baltzell, Tushar R Bhangale, Diana Chang, Amy Dressen, Brian L Yaspan, Ward Ortmann, Matthew J Brauer, Julie Hunkapiller, Jens Reeder, Kiran Mukhyala, Karen T Cuenco, Jennifer A Tom, Amy Cowgill, Jan Vogel, William F Forrest, Timothy W Behrens, Robert R Graham, Arthur Wuster
In clinical trials, a placebo response refers to improvement in disease symptoms arising from the psychological effect of receiving a treatment rather than the actual treatment under investigation. Previous research has reported genomic variation associated with the likelihood of observing a placebo response, but these studies have been limited in scope and have not been validated. Here, we analyzed whole-genome sequencing data from 784 patients undergoing placebo treatment in Phase III Asthma or Rheumatoid Arthritis trials to assess the impact of previously reported variation on patient outcomes in the placebo arms and to identify novel variants associated with the placebo response...
March 18, 2018: Genes and Immunity
Laura Watts, Tugce Karaderi, Amity Roberts, Louise Appleton, Tom Wordsworth, Carla Cohen, Paul Wordsworth, Matteo Vecellio
Genetic polymorphism (rs1800693) of TNFRSF1A (type 1 tumour necrosis factor receptor) encodes a potentially anti-inflammatory soluble truncated form of the p55 receptor, which is associated with predisposition to multiple sclerosis but protection against ankylosing spondylitis (AS). We analysed 2917 UK Caucasian cases by linear and logistic regression for associations of rs1800693 with disease severity assessed by the Bath Ankylosing Spondylitis measures of disease activity and function (BASDAI, BAS-G and BASFI) and/or responses to anti-TNF therapy...
March 10, 2018: Genes and Immunity
Sarah E Kleinstein, Patrick R Shea, Andrew S Allen, David M Koelle, Anna Wald, David B Goldstein
Herpes simplex virus type 2 (HSV-2) is an incurable viral infection with severity ranging from asymptomatic to frequent recurrences. The viral shedding rate has been shown as a reproducible HSV-2 severity end point that correlates with lesion rates. We used a genome-wide association study (GWAS) to investigate the role of common human genetic variation in HSV-2 severity. We performed a GWAS on 223 HSV-2-positive participants of European ancestry. Severity was measured by viral shedding rate, as defined by the percent of days PCR+ for HSV-2 DNA over at least 30 days...
February 28, 2018: Genes and Immunity
Kristin M Olson, Jianming Tang, LaDraka' Brown, Christen G Press, William M Geisler
Associations between human leukocyte antigen (HLA) variants and chlamydia-related outcomes have been inconsistent. We previously identified HLA-DQB1*06 as a risk marker for chlamydia reinfection in a cohort of predominately HIV-infected adolescents. As chlamydia reinfection can lead to reproductive complications, validation of this finding in HIV-seronegative women may help reveal the underlying biology. We performed HLA-DQB1 genotyping in HIV-seronegative, chlamydia-infected African American women who were evaluated for reinfection at 3- and 6-month visits after treatment...
February 26, 2018: Genes and Immunity
Jianfeng Wu, Sirui Yang, Di Yu, Wenjing Gao, Xianjun Liu, Kun Zhang, Xueqi Fu, Wanguo Bao, Kaiyu Zhang, Jiaao Yu, Liankun Sun, Shaofeng Wang
Genetic variants near the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3) at the chromosomal region 6q23 demonstrated significant associations with multiple autoimmune diseases. The signals of associations have been explained to the TNFAIP3 gene, the most likely causal gene. In this study, we employed CRISPR/cas9 genome-editing tool to generate cell lines with deletions including a candidate causal variant, rs6927172, at 140 kb upstream of the TNFAIP3 gene. Interestingly, we observed alterations of multiple genes including IL-20RA encoding a subunit of the receptor for interleukin 20...
February 23, 2018: Genes and Immunity
Marcia Arenas-Hernandez, Nardhy Gomez-Lopez, Valeria Garcia-Flores, Claudia Rangel-Escareño, Luis M Alvarez-Salas, Natalia Martinez-Acuña, Joel A Vazquez-Perez, Rodrigo Vega-Sanchez
Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes...
January 24, 2018: Genes and Immunity
Yiqin Wang, Murad Alahdal, Jia Ye, Liangliang Jing, Xiaoxin Liu, Huan Chen, Liang Jin, Rongyue Cao
GnRH and VEGF have been investigated as prostate carcinoma enhancers that support tumor spread and progression. Although both have documented roles in prostate carcinoma and many cancer types, the weak immunogenicity of these peptides has remained a major challenge for use in immunotherapy. Here, we describe a novel strategy to inhibit GnRH and VEGF production and assess the effect on the immune responses against these hormones using the RM-1 prostate cancer model. We designed a novel recombinant fusion protein which combined GnRH and VEGF as a vaccine against this tumor...
January 23, 2018: Genes and Immunity
Maneesh K Misra, Vincent Damotte, Jill A Hollenbach
Binding of small molecules in the human leukocyte antigen (HLA) peptide-binding groove may result in conformational changes of bound peptide and an altered immune response, but previous studies have not considered a potential role for endogenous metabolites. We performed virtual screening of the complete Human Metabolite Database (HMDB) for docking to the multiple sclerosis (MS) susceptible DRB1*15:01 allele and compared the results to the closely related yet non-susceptible DRB1*15:03 allele; and assessed the potential impact on binding of human myelin basic peptide (MBP)...
January 20, 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
We investigated association between HLA class I and class II alleles and haplotypes, and KIR loci and their HLA class I ligands, with multiple sclerosis (MS) in 419 European American MS patients and 412 ethnically matched controls, using next-generation sequencing. The DRB1*15:01~DQB1*06:02 haplotype was highly predisposing (odds ratio (OR) = 3.98; 95% confidence interval (CI) = 3-5.31; p-value (p) = 2.22E-16), as was DRB1*03:01~DQB1*02:01 (OR = 1.63; CI = 1.19-2.24; p = 1.41E-03). Hardy-Weinberg (HW) analysis in MS patients revealed a significant DRB1*03:01~DQB1*02:01 homozyote excess (15 observed; 8...
January 8, 2018: Genes and Immunity
S Ramgopal, C Rathika, R Padma Malini, V Murali, K Arun, K Balakrishnan
The HLA-DQB1* region exhibits complex associations with autoimmune thyroid disease (AITD). AITD patients (Hashimoto's thyroiditis, HT = 180; Graves' disease, GD = 55) and age/sex matched controls (n = 235) were genotyped for DQB1* alleles by PCR-SSP. Alleles DQB1*02:02, *06:03, *06:09, *03:02, and *03:03 showed an increased risk and *02:01, *05:02, and *06:02 showed a protection toward AITD. Multiple sequence alignment was used to find out the amino acid variations within the peptide-binding pockets of susceptible and/or protective DQB1* alleles...
January 8, 2018: Genes and Immunity
Camilo Andrés Pérez-Romero, Isaura Pilar Sánchez, Laura Naranjo-Piedrahita, Julio Cesar Orrego-Arango, Carlos Enrique Muskus-López, Winston Rojas-Montoya, Jose Luis Franco Restrepo, Claudia Milena Trujillo-Vargas
Polymorphic variants p.66L>R/H (g.7081T>G/A; rs10127939) and p.176F>V (g.10872T>G; rs396991) in FCGR3A (CD16A) have been associated with defects in cytotoxic function of natural killer (NK) cells in humans. Genotyping of these variants in genomic DNA has been ambiguous because of high degree of homology between FCGR3A and FCGR3B. We designed a strategy to genotype these polymorphisms and to evaluate their effects on NK cells' cytotoxic activity. One hundred and fifteen individuals from different geographical regions of Colombia were included...
January 5, 2018: Genes and Immunity
Ning Yu, Sylviane Lambert, Joshua Bornstein, Rajan P Nair, Charlotta Enerbäck, James T Elder
The TRAF3IP2 gene resides within one of at least 63 psoriasis susceptibility loci and encodes Act1, an adapter protein involved in IL-17 receptor and CD40 signaling pathways. TRAF3IP2 is distinctive (among <10% of candidate susceptibility genes) in that a strongly disease-associated variant encodes a missense SNP predicted to be functionally relevant (SNP rs33980500 C/T encoding Act1 pD10N). As assessed by flow cytometry, Act1 protein was expressed at the highest levels in monocytes, with lower levels in T-cells and B-cells...
January 5, 2018: Genes and Immunity
Kozo Ohkusu-Tsukada, Tadashi Yamashita, Teruyo Tsukada, Kimimasa Takahashi
Environmental factors and the major histocompatibility complex (MHC) are involved in the pathogenesis of atopic dermatitis (AD). However, MHC type (H2 haplotype) of AD model mice NC/Nga is poorly understood. Alloreactive CD8+ or CD4+ T cells in NC/Nga strongly responded to each antigen-presenting cells (A/J: H-2a, C57BL/6: H-2b, BALB/c: H-2d, or C3H/HeJ: H-2k), suggesting that NC/Nga has other H2 haplotype. Polymorphic microsatellite (CA)n repeats in TNF-α gene differ based on the H2 haplotype at present. NC/Nga's (CA)n repeats (n = 19) were different from other examined strains, A/J (n = 14), BALB/c (n = 14), C3H/HeJ (n = 16), and C57BL/6 (n = 20)...
December 22, 2017: Genes and Immunity
Joong-Gon Shin, Hyun Sub Cheong, Jason Yongha Kim, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Jae Youn Cheong, Sung Won Cho, Neung Hwa Park, Suhg Namgoong, Lyoung Hyo Kim, Yoon Jun Kim, Hyoung Doo Shin
Chronic hepatitis B (CHB) is a precursor to liver cirrhosis and hepatocellular carcinoma, caused by a Hepatitis B viral infection. Genome-wide association studies (GWASs) have been conducted to find genes associated with CHB risk. In previous GWAS, EHMT2 was identified as one of the susceptibility genes for CHB. To further characterize this association and discover possible causal variants, we conducted an additional association study. A total of 11 EHMT2 single-nucleotide polymorphisms (SNP) were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 controls)...
December 14, 2017: Genes and Immunity
Line Lykke Andersen, Ewa Terczyńska-Dyla, Nanna Mørk, Carsten Scavenius, Jan J Enghild, Klara Höning, Veit Hornung, Mette Christiansen, Trine H Mogensen, Rune Hartmann
We selected two sets of naturally occurring human missense allelic variants within innate immune genes. The first set represented eleven non-synonymous variants in six different genes involved in interferon (IFN) induction, present in a cohort of patients suffering from herpes simplex encephalitis (HSE) and the second set represented sixteen allelic variants of the IFNLR1 gene. We recreated the variants in vitro and tested their effect on protein function in a HEK293T cell based assay. We then used an array of 14 available bioinformatics tools to predict the effect of these variants upon protein function...
December 4, 2017: Genes and Immunity
X B Wang, J J Ellis, D J Pennisi, X Song, J Batra, K Hollis, L A Bradbury, Z Li, T J Kenna, M A Brown
Tumor necrosis factor-α (TNF-α) inhibitors are highly effective in suppressing inflammation in ankylosing spondylitis (AS) patients, and operate by suppression of TFN-α and downstream immunological pathways. To determine the mechanisms of action of TNF-α inhibitors in AS patients, we used transcriptomic and bioinformatic approaches on peripheral blood mononuclear cells from AS patients pre and post treatment. We found 656 differentially expressed genes, including the genome-wide significant AS-associated genes, IL6R, NOTCH1, IL10, CXCR2 and TNFRSF1A...
September 2017: Genes and Immunity
T Nikolic, N J C Woittiez, A van der Slik, S Laban, A Joosten, C Gysemans, C Mathieu, J J Zwaginga, B Koeleman, B O Roep
Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD3/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators...
September 2017: Genes and Immunity
J Karami, M Mahmoudi, A Amirzargar, M Gharshasbi, A Jamshidi, S Aslani, M H Nicknam
Methylation of DNA is one of the important regulatory mechanisms of gene transcription. B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) plays a key role in the development, proliferation, differentiation, and survival of T cells. The aim of this study was to evaluate promoter methylation of BCL11B gene and its mRNA level in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients in relation to healthy controls and evaluate their correlation with diseases clinical indices...
September 2017: Genes and Immunity
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