Protection against rheumatoid arthritis by HLA: nature and nurture
Protection against rheumatoid arthritis by HLA: nature and nurture
复制标题
DOI：
10.1136/ard.2008.098509
复制
发表时间：
2008-12-01
影响因子：
27.4
通讯作者：
Toes, R. E. M.
中科院分区：
文献类型：
--
作者：
Feitsma, A. L.;van der Helm-van Mil, A. H. M.;Toes, R. E. M.
类风湿性关节炎 (RA) 是一种复杂的遗传性疾病，其中 HLA 区域对遗传风险贡献最大。在 DRB1 链第三个高变区的位置 70-74 处含有氨基酸序列 QKRAA/QRRAA/RRRAA（即 HLA-DRB1*0101、*0102、*0401、*0404、*0405、*0408、*0410、*1001 和 *1402）的 HLA-DRB1 分子与对以下疾病的易感性相关： RA。在同一位置含有氨基酸“DERAA”（即 HLA-DRB1*0103、*0402、*1102、*1103、*1301、*1302 和 *1304）的 HLA-DRB1 分子与 RA 的保护作用相关。有趣的是，不仅来自母亲的遗传性 HLA 抗原也会影响 RA 易感性。最近描述了含有“DERAA”的 HLA-DRB1 等位基因作为非遗传性母体抗原 (NIMA)。这种保护作用的根本机制目前尚不清楚，尽管下面介绍了可能的解释。在本综述中，概述了当前有关 RA 预防的知识，并比较了包含“DERAA”的 HLA-DRB1 等位基因的遗传效应和 NIMA 效应。
Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70-74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA'' ( ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA''-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA''-containing HLA-DRB1 alleles are compared.