New insights into the pathogenesis and genetics of psoriatic arthritis.
New insights into the pathogenesis and genetics of psoriatic arthritis.
复制标题
DOI：
10.1038/ncprheum0987
复制
发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Bowcock, Anne M.
中科院分区：
文献类型：
--
作者：
Nograles, Kristine E.;Brasington, Richard D.;Bowcock, Anne M.
银屑病（Psoriasis， PS）与银屑病关节炎（psoriatic arthritis， PSA）是相互关联的遗传性疾病。银屑病皮肤的特点是过度增生，角质形成细胞分化差和强烈的单核炎症。银屑病关节的特点是滑膜和关节高度发炎，软骨和骨有局灶性糜烂。最近的遗传分析发现了PS和PsA共有的危险因素。就常见变异而言，HLA I类区域是PS和PsA易感性最强的位点。其他危险因素暗示il - 23途径和Th17细胞的诱导/调节在这两种疾病的发病机制中。IL22和IL等细胞因子的细化可导致角质形成细胞和潜在的滑膜细胞的超增殖表型，导致皮肤和关节增殖/炎症的恶性循环。在滑膜组织中，疾病相关的细胞因子也可能导致RANK配体依赖的破骨细胞形成，从而导致骨侵蚀。需要明确导致PsA的遗传风险因素。针对肿瘤坏死因子的治疗在治疗这两种疾病中经常非常成功，并且遗传研究结果可能导致针对个体遗传特征定制的额外治疗的发展。
Psoriasis (PS) and psoriatic arthritis (PSA) are inter-related heritable diseases. Psoriatic skin is characterized by hyperproliferative, poorly differentiated keratinocytes and robust mononuclear inflammation. Psoriatic joints are characterized by highly inflamed synovia and entheses with focal erosions of cartilage and bone. Recent genetic analyses have uncovered risk factors shared by both PS and PsA. With respect to common variation, the HLA class I region is the locus that predisposes most strongly to PS and PsA. Other risk factors implicate the IL23 pathway and the induction/regulation of Th17 cells in the pathogenesis of both diseases. Elaboration by cytokines such as IL22 and IL could result in the hyper-proliferative phenotype of keratinocytes and potentially synoviocytes, leading to the vicious cycle of proliferation/inflammation in both the skin and joints. In synovial tissue, disease-related cytokines may also lead to RANK ligand dependent osteoclast formation leading to bone erosion. Genetic risk factors leading specifically to PsA need to be identified. Therapies targeting TNF have frequently been highly successful in the treatment of both diseases, and genetic findings are likely to lead to the development of additional treatments tailored to an individual’s genetic profile.
登录
查看更多内容
影响因子：
13.8
作者：
Gelfand, JM;Stern, RS;Margolis, DJ
通讯作者：
Margolis, DJ
影响因子：
2.7
作者：
Gladman, DD;Cheung, C;Wade, JA
通讯作者：
Wade, JA
影响因子：
4.4
作者：
Albanesi, Cristina;Fairchild, Heather R.;Howell, Michael D.
通讯作者：
Howell, Michael D.
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
影响因子：
9.8
作者：
Cargill, Michele;Schrodi, Steven J.;Begovich, Ann B.
通讯作者：
Begovich, Ann B.