HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course
HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course
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DOI：
10.1086/367781
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发表时间：
2003-03-01
影响因子：
9.8
通讯作者：
Hauser, SL
中科院分区：
文献类型：
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作者：
Barcellos, LF;Oksenberg, JR;Hauser, SL
多发性硬化症（MS）的疾病易感性模型通常假设HLA-DRB 1 * 1501等位基因及其相关单倍型（DRB 1 * 1501-DQB 1 * 0602或DR 2）起主导作用。使用稳健且表型良好表征的MS数据集更详细地探索该模型。HLA-DR 2单倍型对MS易感性有剂量效应。这一观察结果表明，除了HLA-DR 2在MS中的作用外，易感性单倍型的两个拷贝进一步增加疾病风险。其次，我们报告DR 2单倍型修饰疾病表达。在DR 2纯合子个体中，良性MS很少，严重MS增加。人类白细胞抗原（HLA）区域与MS的联系和关联的分子机制的概念需要修改以适应这些数据。
Models of disease susceptibility in multiple sclerosis (MS) often assume a dominant action for the HLA-DRB1* 1501 allele and its associated haplotype (DRB1* 1501-DQB1* 0602 or DR2). A robust and phenotypically well-characterized MS data set was used to explore this model in more detail. A dose effect of HLA-DR2 haplotypes on MS susceptibility was revealed. This observation suggests that, in addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype further increase disease risk. Second, we report that DR2 haplotypes modify disease expression. There is a paucity of benign MS and an increase of severe MS in individuals homozygous for DR2. Concepts of the molecular mechanisms that underlie linkage and association of the human leukocyte antigen (HLA) region to MS need to be revised to accommodate these data.