The rheumatoid arthritis HLA-DRB1 shared epitope.
The rheumatoid arthritis HLA-DRB1 shared epitope.
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DOI：
10.1097/bor.0b013e328336ba63
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发表时间：
2010-05
影响因子：
5.1
通讯作者：
Holoshitz J
中科院分区：
文献类型：
--
作者：
Holoshitz J
更新2008年12月至2009年11月期间关于类风湿关节炎（RA）共有表位（SE）在RA病因和发病机制中的作用的进展。最近提出的新证据表明，通过妊娠或在子宫内暴露于母体抗原而产生的非遗传性HLA抗原可能有助于SE阴性妇女发生RA。吸烟与SE编码的非 *04 HLA-DRB 1等位基因（特别是HLA-DRB 1 *01和HLA-DRB 1 *10）之间的相互作用首次正式确立。在确定SE、PTPN 22和吸烟在抗瓜氨酸化蛋白抗体（ACPA）阳性和阴性RA风险中的相对贡献和相互作用方面取得了进展。ACPA在相当数量的RA患者中识别的自身抗原已被鉴定为瓜氨酸化α烯醇化酶，并且遗传因素在ACPA阴性RA中的重要性已被强调。此外，RA风险与几个新的遗传标记的关联已被报道。其中：2个新的MHC，非DRB 1位点，MHC I类多肽相关序列A（云母）的多态性标记，Fcγ受体的等位基因; β2肾上腺素能受体的多态性标记，细胞色素P450亚型1A 2的低诱导等位基因。虽然SE-RA关联的机制基础仍然是一个谜，但在过去一年中进行的观察揭示了SE -单独或与其他基因或环境因素组合-影响RA风险和疾病表型的条件。
To update progress made between December 2008 and November 2009 on the role of the rheumatoid arthritis (RA) shared epitope (SE) in the etiology and pathogenesis of RA. New evidence has been recently presented to suggest that non-inherited HLA antigens originating through pregnancy or exposure to maternal antigens in utero could contribute to RA development in SE-negative women. An interaction between smoking and SE-coding non-*04 HLA-DRB1 alleles (particularly HLA-DRB1*01 and HLA-DRB1*10) was formally established for the first time. Progress has been made in determining the relative contributions and the interaction of the SE, PTPN22 and smoking in conferring the risk of anti-citrullinated protein antibodies (ACPA)-positive and –negative RA. The autoantigen which ACPA recognize in a significant number of RA patients has been identified as citrullinated α enolase and the importance of genetic factors in ACPA-negative RA has been highlighted. Additionally, associations of RA risk with several new genetic markers have been reported. Among them: 2 new MHC, non-DRB1loci, a polymorphism marker in MHC class I polypeptide-related sequence A (MICA), an allele of the Fcγ receptor; a polymorphism marker in the β2 adrenergic receptor and a low-inducible allele of the cytochrome P450 subtype 1A2. While the mechanistic basis of SE-RA association remain an enigma, observations made during the last year shed new light on the conditions in which the SE - alone or in combination with other genes or environmental factors - affects the risk of RA and the phenotype of the disease.