Izzotti Alberto, Longobardi Mariagrazia, Cartiglia Cristina, Anzuini Francesco, Arrigo Patrizio, Fazzi Elisa, Orcesi Simona, Piana Roberta La, Pulliero Alessandra
Department of Health Sciences, University of Genoa, Genoa, 16132, Italy.
J Child Neurol. 2012 Jan;27(1):51-60. doi: 10.1177/0883073811413582. Epub 2011 Aug 23.
Aicardi-Goutières syndrome is a rare encephalopathy of mutational origin characterized by increased levels of interferon alpha in cerebrospinal fluid. The aim of this study was to explore the influence of different Aicardi-Goutières syndrome genotypes on the clinical course of patients, seeking to identify specific gene expression profiles able to explain Aicardi-Goutières syndrome phenotype differences. We detected the occurrence of Aicardi-Goutières syndrome mutations in 21 patients and compared microarray gene-expression data of cerebrospinal fluid lymphocytes with clinical variables. The levels of interferon alpha in cerebrospinal fluid were high in all patients; we found differences in the expression of genes encoding for Toll-like receptor, endogenous RNases, T lymphocyte activation, angiogenesis inhibition, and peripheral interferon alpha production. These results indicate that further to interferon alpha production in the central nervous system, a variety of other pathogenic mechanisms is activated in Aicardi-Goutières syndrome to various degrees in different patients, thus explaining the interindividual difference in Aicardi-Goutières syndrome course.
艾卡迪-古铁雷斯综合征是一种由突变引起的罕见脑病，其特征是脑脊液中α干扰素水平升高。本研究的目的是探讨不同艾卡迪-古铁雷斯综合征基因型对患者临床病程的影响，试图识别能够解释艾卡迪-古铁雷斯综合征表型差异的特定基因表达谱。我们检测了21例患者中艾卡迪-古铁雷斯综合征突变的发生情况，并将脑脊液淋巴细胞的微阵列基因表达数据与临床变量进行了比较。所有患者脑脊液中的α干扰素水平都很高；我们发现了编码Toll样受体、内源性核糖核酸酶、T淋巴细胞活化、血管生成抑制和外周α干扰素产生的基因在表达上存在差异。这些结果表明，除了中枢神经系统中α干扰素的产生外，艾卡迪-古铁雷斯综合征还会在不同患者中不同程度地激活多种其他致病机制，从而解释了艾卡迪-古铁雷斯综合征病程的个体差异。
