Developments in the scientific understanding of rheumatoid arthritis.
Developments in the scientific understanding of rheumatoid arthritis.
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DOI：
10.1186/ar2758
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发表时间：
2009
影响因子：
4.9
通讯作者：
Weyand CM
中科院分区：
文献类型：
--
作者：
Goronzy JJ;Weyand CM
风湿性关节炎（RA）是一种自身免疫性疾病，可引起临床前全身异常，最终导致滑膜炎症和关节结构破坏。最近确定的遗传风险因素和新的见解，从动物模型的自发性关节炎的胸腺选择的自身反应性T细胞库是一个重要的危险因素，这种疾病的概念提供了支持。随着年龄的增长，T细胞库的稳态控制和信号传导阈值设置的缺陷导致促炎性T效应细胞群的积累和对新抗原（如瓜氨酸化肽）的耐受性丧失。由于对修饰的自身抗原的耐受性的破坏可以在滑膜炎之前几十年，稳态缺陷的修复可能为RA的预防性干预打开一个独特的机会之窗。RA的最终结果，软骨和骨的破坏，似乎是由细胞因子和细胞接触诱导的滑膜细胞和单核细胞的活化驱动的，其中一些分化成组织破坏性破骨细胞。靶向参与这一过程的介质大大改善了这种慢性炎症综合征的管理。
Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome.
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影响因子：
4.9
作者：
Cope AP
通讯作者：
Cope AP
DOI：
10.1186/ar557
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Cope AP
通讯作者：
Cope AP
影响因子：
30.5
作者：
Boone, DL;Turer, EE;Ma, A
通讯作者：
Ma, A
影响因子：
--
作者：
Barton, A;Bowes, J;Worthington, J
通讯作者：
Worthington, J
DOI：
10.1186/ar558
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Burger D;Dayer JM
通讯作者：
Dayer JM