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首页> 外文期刊>Journal of neuroinflammation >Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response
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Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response

机译：干扰素-γ和趋化因子基因的差异表达将拉斯穆森脑炎与皮质发育异常区分开，并为早期Th1免疫反应提供了证据

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Background Rasmussen encephalitis (RE) is a rare complex inflammatory disease, primarily seen in young children, that is characterized by severe partial seizures and brain atrophy. Surgery is currently the only effective treatment option. To identify genes specifically associated with the immunopathology in RE, RNA transcripts of genes involved in inflammation and autoimmunity were measured in brain tissue from RE surgeries and compared with those in surgical specimens of cortical dysplasia (CD), a major cause of intractable pediatric epilepsy. Methods Quantitative polymerase chain reactions measured the relative expression of 84 genes related to inflammation and autoimmunity in 12 RE specimens and in the reference group of 12 CD surgical specimens. Data were analyzed by consensus clustering using the entire dataset, and by pairwise comparison of gene expression levels between the RE and CD cohorts using the Harrell-Davis distribution-free quantile estimator method. Results Consensus clustering identified six RE cases that were clearly distinguished from the CD cases and from other RE cases. Pairwise comparison showed that seven mRNAs encoding interferon-γ, CCL5, CCL22, CCL23, CXCL9, CXCL10, and Fas ligand were higher in the RE specimens compared with the CD specimens, whereas the mRNA encoding hypoxanthine-guanine phosphoribosyltransferase was reduced. Interferon-γ, CXCL5, CXCL9 and CXCL10 mRNA levels negatively correlated with time from seizure onset to surgery (P <0.05), whereas CCL23 and Fas ligand transcript levels positively correlated with the degree of tissue destruction and inflammation, respectively (P <0.05), as determined from magnetic resonance imaging (MRI) T2 and FLAIR images. Accumulation of CD4+ lymphocytes in leptomeninges and perivascular spaces was a prominent feature in RE specimens resected within a year of seizure onset. Conclusions Active disease is characterized by a Th1 immune response that appears to involve both CD8+ and CD4+ T cells. Our findings suggest therapeutic intervention targeting specific chemokine/chemokine receptors may be useful in early stage RE.
机译：背景拉斯穆森脑炎（RE）是一种罕见的复杂炎症性疾病，主要见于幼儿，其特征是严重的部分性癫痫发作和脑萎缩。手术是目前唯一有效的治疗选择。为了鉴定与RE的免疫病理学特异性相关的基因，在RE手术的脑组织中测量了与炎症和自身免疫有关的基因的RNA转录本，并将其与皮质发育不良（CD）的手术标本进行了比较，后者是顽固性小儿癫痫的主要原因。方法采用定量聚合酶链反应，在12例RE标本和12例CD手术标本的参考组中，测定了与炎症和自身免疫相关的84个基因的相对表达。通过使用整个数据集的共识聚类分析数据，并通过使用Harrell-Davis无分布分位数估计方法对RE和CD队列之间的基因表达水平进行成对比较。结果共识聚类确定了6个与CD案件和其他RE案件明显区分开的RE案件。配对比较显示，与CD标本相比，RE标本中编码干扰素-γ，CCL5，CCL22，CCL23，CXCL9，CXCL10和Fas配体的7个mRNA较高，而编码次黄嘌呤-鸟嘌呤磷酸核糖基转移酶的mRNA减少。干扰素-γ，CXCL5，CXCL9和CXCL10 mRNA水平与癫痫发作至手术时间呈负相关（P <0.05），而CCL23和Fas配体转录物水平与组织破坏和炎症程度呈正相关（P <0.05）由磁共振成像（MRI）T2和FLAIR图像确定。在癫痫发作一年内切除的RE标本中，软脑膜和血管周间隙中CD4 +淋巴细胞的积累是一个突出特征。结论活动性疾病的特征是Th1免疫反应，似乎涉及CD8 +和CD4 + T细胞。我们的发现表明，针对特定趋化因子/趋化因子受体的治疗干预可能在早期RE中有用。

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