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Peripheral Blood Eosinophilia and Long-term Severity in Pediatric-Onset Inflammatory Bowel Disease.

儿童发病的炎症性肠病的外周血嗜酸性粒细胞增多和长期严重程度。

  • 影响因子:3.72
  • 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
  • 发表时间:2020-01-21
Abstract

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.

摘要

背景:外周血嗜酸性粒细胞增多症(PBE)是成人炎症性肠病(IBDs)侵袭性多年自然史的生物标志物。此外,诊断时的PBE与儿童起病IBD中较高的疾病活动性相关。我们试图确定PBE是否可以作为跟踪到成年的儿童起病IBD患者长期疾病严重程度的生物标记物。 方法:我们分析了2009年至2018年在一所成人高等教育中心进行的同意的、前瞻性的、自然史IBD登记。对儿童和成人起病的IBD患者进行PBE患病率评估。比较有和无PBE患者的人口统计学、临床特征和卫生保健利用数据。 结果:2800例成人IBD患者中,23.4%有小儿起病。34%的儿童起病患者与26.8%的成人起病IBD患者存在PBE(P<0.001)。在儿童起病的IBD队列中,PBE与较高的过敏率相关(P<0.0001),但与哮喘、过敏性鼻炎或原发性硬化性胆管炎无关。在儿童起病的成人IBD患者中,PBE与C-反应蛋白升高(P<0.0001)、血沉升高(P<0.0001)、医疗利用率和年平均医疗费用升高(P<0.00001)相关。 结论:成人IBD患儿外周血嗜酸性粒细胞增多症较成人发病率高。在所有长期随访的IBD患者中,PBE定义了病情较重的亚组。这些数据表明,PBE可能是一个高风险亚组的生物标记物,该亚组在持续到成年的儿童起病IBD中具有高成本和长期的严重性。

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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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