Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis
Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis
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DOI：
10.1172/jci200523661
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发表时间：
2005-05-01
影响因子：
15.9
通讯作者：
Hemmer, B
中科院分区：
文献类型：
--
作者：
Cepok, S;Zhou, D;Hemmer, B
MS是一种慢性炎症性和CNS脱髓鞘性疾病，其病因尚不清楚。这种疾病的一个标志是脑脊液（CSF）中出现寡克隆IgG抗体。为了评估这些抗体的特异性，我们筛选了含有37，000个标记蛋白质的蛋白质表达阵列。进一步绘制了2种最常见的MS特异性反应性，以鉴定潜在的高亲和力表位。在这两种情况下，我们确定了来自潜伏感染细胞中表达的EBV蛋白的肽序列。这些EBV蛋白，BRRF 2和EBNA-1的免疫反应性，MS患者的血清和CSF中显着高于对照供体。来自MS患者的寡克隆CSF IgG特异性结合两种EBV蛋白。此外，MS患者的CD 8（+）T细胞对潜伏EBV蛋白的反应高于对照组。总之，这些发现表明MS患者对EBV的免疫应答增加，这表明病毒在疾病的发病机制中起着重要作用。
MS is a chronic inflammatory and demyelinating disease of the CNS with as yet unknown etiology. A hallmark of this disease is the occurrence of oligoclonal IgG antibodies in the cerebrospinal fluid (CSF). To assess the specificity of these antibodies, we screened protein expression arrays containing 37,000 tagged proteins. The 2 most frequent MS-specific reactivities were further mapped to identify the underlying high-affinity epitopes. In both cases, we identified peptide sequences derived from EBV proteins expressed in latently infected cells. Immunoreactivities to these EBV proteins, BRRF2 and EBNA-1, were significantly higher in the serum and CSF of MS patients than in those of control donors. Oligoclonal CSF IgG from MS patients specifically bound both EBV proteins. Also, CD8(+) T cell responses to latent EBV proteins were higher in MS patients than in controls. In summary, these findings demonstrate an increased immune response to EBV in MS patients, which suggests that the virus plays an important role in the pathogenesis of disease.