A striking local esophageal cytokine expression profile in eosinophilic esophagitis.
A striking local esophageal cytokine expression profile in eosinophilic esophagitis.
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DOI：
10.1016/j.jaci.2010.10.039
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
Blanchard C;Stucke EM;Rodriguez-Jimenez B;Burwinkel K;Collins MH;Ahrens A;Alexander ES;Butz BK;Jameson SC;Kaul A;Franciosi JP;Kushner JP;Putnam PE;Abonia JP;Rothenberg ME
嗜酸性粒细胞性食管炎（EE）是一种新兴的世界性疾病，类似于胃食管反流病。早期研究表明，食管嗜酸性粒细胞增多与辅助性T型2型过敏反应有关，但相关细胞因子的局部和全身表达尚未得到很好的表征。采用包含84个基因的人炎症细胞因子和受体PCR阵列，然后采用PCR验证和多重阵列来量化食管活检和血液中细胞因子mRNA的水平。许多趋化因子[如CCL1、CCL23、CCL26 （eotaxin-3）、CXCL1和CXCL2]、细胞因子（如IL13和ABCF1）和细胞因子受体（如IL5RA）的食道转录物在EE患者中被诱导至少4倍。食道活检分析（n=288）显示，仅eotaxin-3 mRNA水平区分EE与非EE个体的敏感性为89%。过敏的存在与活动期EE患者食管IL4和IL5 mRNA表达显著升高相关。我们鉴定了8种细胞因子（IL-4、IL-13、IL-5、IL-6、IL-12p70、CD40L、IL-1α和IL-17），它们的血液水平回顾性区分了12例非EE患者和13例EE患者，特异性和敏感性均为100%。当应用于一组盲法、前瞻性招募的36名患者时，细胞因子小组评分系统在识别EE方面的阳性预测值为79%，阴性预测值为68%，敏感性为61%，特异性为83%。有证据表明，IL13和IL5与嗜酸性粒细胞和eotaxin-3水平相关，表明适应性Th2免疫在没有细胞因子一致的系统性变化的情况下调节eotaxin-3驱动的食管嗜酸性粒细胞的关键作用。
Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Early studies have suggested that esophageal eosinophilia occurs in association with T helper type 2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood levels. Esophageal transcripts of numerous chemokines [e.g. CCL1, CCL23, CCL26 (eotaxin-3), CXCL1, and CXCL2], cytokines (e.g. IL13 and ABCF1), and cytokine receptors (e.g. IL5RA) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n=288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing EE from non-EE individuals. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in active EE patients. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40L, IL-1α, and IL-17) whose blood levels retrospectively distinguished 12 non-EE from 13 EE patients with 100% specificity and 100% sensitivity. When applied to a blinded, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive Th2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines.
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DOI：
10.1097/01.mpg.0000188740.38757.d2
发表时间：
2006-01-01
影响因子：
2.9
作者：
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通讯作者：
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影响因子：
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通讯作者：
Rothenberg, Marc E.
影响因子：
15.9
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