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Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients.

克罗恩病患者全基因组单核苷酸多态性与 MR 小肠造影特征之间的新型相关性。

  • 影响因子:3.96
  • DOI:10.1002/jmri.27250
  • 作者列表:"Cruz-Romero C","Guo A","Bradley WF","Vicentini JRT","Yajnik V","Gee MS
  • 发表时间:2020-06-18
Abstract

BACKGROUND:Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known. PURPOSE:To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging. STUDY TYPE:Retrospective. POPULATION:54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease. FIELD STRENGTH/SEQUENCE:1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, T2 -weighted fast spin echo fat-suppressed, and T1 -weighted fat-suppressed pre- and postcontrast imaging. ASSESSMENT:Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively. STATISTICAL TESTS:Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant. RESULTS:MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014). DATA CONCLUSION:This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging. LEVEL OF EVIDENCE:3 TECHNICAL EFFICACY STAGE: 2.

摘要

背景: 患者基因多态性与克罗恩的临床行为相关; 然而,其与磁共振小肠造影 (MRE) 成像表现的相关性尚不清楚。 目的: 分析一组已知的克罗恩病 (CD) 相关单核苷酸多态性与 MRE 成像表型和成像频率的相关性。 研究类型: 回顾性。 人群: 54 名患者 (平均年龄 40 岁; 32 名女性和 22 名男性) 2009 年至 2016 年建立的 CD,对 168 个可能与炎症性肠病相关的单核苷酸多态性 (SNPs) 进行基线 MRE 和基因检测。 场强/序列: 1.5T 或 3T 临床扫描仪,标准 MRE 临床脉冲序列,包括 T2 加权单次激发快速自旋回波,平衡稳态自由进动,t2 加权快速自旋回波脂肪抑制,T1 加权脂肪抑制造影前后成像。 评估: 三名读者 (所有身体成像专业人员) 独立评估所有成像是否存在活动性疾病和穿透性并发症。记录内镜检查和横断面成像 (CSI) 的发病日期和频率。分别根据维也纳和蒙特利尔分类对疾病行为和分布进行分类。 统计检验: 分别采用 Student t 检验和 Fisher 精确检验评估连续变量和分类变量的显著性。还应用隐马尔可夫模型统计敲除方法分析遗传-成像关联,校正后 P <0.05 认为有意义。 结果: MRE 在 42 例 (78%) 患者中表现为活动性肠道炎症,13 例 (28%) 狭窄,13 例 (28%) 瘘管。SNP rs1292053 (RBS6KB1) 与小肠炎症和管腔狭窄高度相关,观察到的相关频率分别为 0.66 和 0.39 (P = 0.001)。rs6062504 (Decoy 受体 3) 与发病年龄较低 (P = 0.012) 、发病早期患者比例较高(P = 0.012),并且更高的平均 CSI 数/年 (P = 0.014)。 数据结论: 本研究证明了 CD 基因型与 MRE 表型和横断面成像频率之间存在显著相关性。 证据级别: 3 技术疗效阶段: 2.

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发表时间:2020-01-30
来源期刊:The FEBS journal
DOI:10.1111/febs.15236
作者列表:["Sayed IM","Suarez K","Lim E","Singh S","Pereira M","Ibeawuchi SR","Katkar G","Dunkel Y","Mittal Y","Chattopadhyay R","Guma M","Boland BS","Dulai PS","Sandborn WJ","Ghosh P","Das S"]

METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.

影响因子:3.72
发表时间:2020-01-21
DOI:10.1093/ibd/izz323
作者列表:["Prathapan KM","Ramos Rivers C","Anderson A","Koutroumpakis F","Koutroubakis IE","Babichenko D","Tan X","Tang G","Schwartz M","Proksell S","Johnston E","Hashash JG","Dunn M","Wilson A","Barrie A","Harrison J","Hartman D","Kim SC","Binion DG"]

METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

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影响因子:3.72
发表时间:2020-01-21
DOI:10.1093/ibd/izz331
作者列表:["Ronchetti S","Gentili M","Ricci E","Migliorati G","Riccardi C"]

METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.

关键词: GILZ IBD 自身免疫 炎症
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