The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action.
The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action.
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DOI：
10.2174/138920207783591690
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发表时间：
2007-11
期刊：
影响因子：
2.6
通讯作者：
Simmonds MJ
中科院分区：
文献类型：
--
作者：
Gough SC;Simmonds MJ
HLA区域编码在免疫系统中发挥关键作用的几种分子。HLA区域和自身免疫性疾病（AID）之间的强关联已经建立了50多年。已检测到HLA II类编码的HLA-DRB 1-DQA 1-DQB 1单倍型的组分与几种AIDS（包括类风湿性关节炎、1型糖尿病和Graves病）的关联。由该区域编码的分子在外源性抗原呈递给CD 4 + Th细胞中起关键作用，表明该途径在AID起始和进展中的重要性。尽管HLA I类和III类区域的其他成分也被研究与AID的关联，除了HLA-B*27与强直性脊柱炎的关联之外，很难确定与HLA II类基因的强连锁不平衡（LD）无关的其他易感性位点。LD的统计分析和大型AID数据集的招募的最新进展，允许调查的HLA I类和III类区域被重新访问。HLA I类区域的关联，独立于已知的HLA II类效应，现在已经在几种艾滋病中检测到，包括HLA-B与1型糖尿病和HLA-C与多发性硬化症和格雷夫斯病的强关联。这些结果进一步证明了细菌或病毒感染和CD 8 + T细胞在AID发病中的可能作用。在确定HLA区域和艾滋病的主要关联方面取得的进展不仅将增加我们对疾病发病机制的理解，而且还可能有助于未来开发新的治疗靶点。
The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves’ disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves’ disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.
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DOI：
10.1016/j.clim.2007.02.002
发表时间：
2007-06
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Boucher A;Desforges M;Duquette P;Talbot PJ
通讯作者：
Talbot PJ
DOI：
10.1196/annals.1422.059
发表时间：
2007-01-01
期刊：
AUTOIMMUNITY, PT D
影响因子：
--
作者：
Barzilai, O.;Sherer, Y.;Shoenfeld, Y.
通讯作者：
Shoenfeld, Y.
影响因子：
2.7
作者：
CUCCA, F;MUNTONI, F;CONGIA, M
通讯作者：
CONGIA, M
影响因子：
3.2
作者：
Brand, Oliver J.;Lowe, Christopher E.;Gough, Stephen C. L.
通讯作者：
Gough, Stephen C. L.
影响因子：
3.1
作者：
Ahmed, M. Mubashir;Berney, Seth Mark;King, John W.
通讯作者：
King, John W.