Interferon-Related Transcriptome Alterations in the Cerebrospinal Fluid Cells of Aicardi-Goutieres Patients†
Interferon-Related Transcriptome Alterations in the Cerebrospinal Fluid Cells of Aicardi-Goutieres Patients†
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DOI：
10.1111/j.1750-3639.2008.00229.x
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发表时间：
2009-10-01
期刊：
影响因子：
6.4
通讯作者：
Fazzi, Elisa
中科院分区：
文献类型：
--
作者：
Izzotti, Alberto;Pulliero, Alessandra;Fazzi, Elisa
aicardii - goutieres综合征（AGS）是一种罕见的干扰素（IFN）相关脑病，发病时间为生命的第一年。AGS的临床特征为进行性小头畸形、双侧基底节区钙化、脑萎缩、脑脊液（CSF）、淋巴细胞增多、精神运动能力发育迟缓并伴有锥体-锥体外系综合征，与先天性病毒感染相似。对20例脑脊液中ifn - α水平高的AGS患者（年龄4.5 +/- 4.4岁，平均+/-标准差）和20例匹配对照（年龄4.4 +/- 4.3岁，平均+/-标准差）的脑脊液淋巴细胞进行了检测18880个人类基因表达的微阵列分析。基因表达数据显示，所有对照组和18例AGS病例与对照组之间存在显著差异。与对照组相比，未分类的2例AGS患者年龄均大于7岁。AGS患者表现为ifn依赖性通路和淋巴细胞功能相关基因上调，同时编码血管生成活性的基因下调。胱抑素F和DNAJ基因对IFN通路有负反馈，它们的表达经历了与年龄相关的进行性增加。这些基因表达特征与临床症状随着年龄的增长而逐渐减弱相似。获得的结果提供了暴露于ifn - α对发育中的大脑有害的证据。
Aicardi-Goutieres syndrome (AGS) is a rare interferon (IFN)-related encephalopathy with onset during the first year of life. AGS, is clinically characterized by progressive microcephaly, bilateral basal ganglia calcification, cerebral atrophy, cerebrospinal fluid (CSF), lymphocytosis, delayed development of psychomotor abilities with pyramidal-extrapyramidal syndrome and mimics congenital viral infections. Microarray analysis examining the expression of 18 880 human genes has been applied to the CSF lymphocytes of 20 AGS cases (age 4.5 +/- 4.4 years, mean +/- standard deviation) characterized by high IFN-alpha levels in CSF and 20 matched controls (age 4.4 +/- 4.3 years, mean +/- standard deviation). Gene-expression data reveal significant differences between AGS cases and controls for all controls and 18 AGS cases. The two AGS cases unclassified as compared with controls were both older than 7 years. AGS cases presented upregulation of genes involved in IFN-dependent pathways and lymphocyte functions, paralleled by the downregulation of genes encoding for angiopoietic activities. The cystatin F and DNAJ genes, having a negative feedback on IFN pathways, underwent a progressive age-related increase in their expression. These gene-expression signature parallels a progressive attenuation of clinical symptoms with age. Obtained results provide evidence that exposure to IFN-alpha is harmful for developing brain.