Disease mechanisms in preclinical rheumatoid arthritis: A narrative review.
Disease mechanisms in preclinical rheumatoid arthritis: A narrative review.
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DOI：
10.3389/fmed.2022.689711
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发表时间：
2022
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
在过去的几十年中，临床前类风湿性关节炎（RA）的概念已经确立。事实上，疾病机制在临床RA发作前几年就开始的发现是最近对RA发病机制的理解中的主要见解之一。根据疾病的复杂性，临床前事件延续了几个连续的阶段。在遗传易感宿主中，环境因素将进一步增加对RA事件的易感性。在临床前疾病的最初阶段，免疫紊乱机制发生在关节腔室之外，即在粘膜表面，如肺、牙龈或肠道。在此，对改变的抗原的持续免疫应答将导致耐受性的破坏并触发自身免疫。在第二阶段，免疫应答成熟并在全身水平上被放大，表位扩散并扩大自身抗体库。最后，滑膜和骨隔室被针对修饰抗原的特异性自身抗体靶向，引发局部炎症反应，最终导致临床上明显的滑膜炎。在这篇综述中，我们讨论了详细的疾病机制在临床前RA，提供了一个广阔的前景，根据目前的证据。
In the last decades, the concept of preclinical rheumatoid arthritis (RA) has become established. In fact, the discovery that disease mechanisms start years before the onset of clinical RA has been one of the major recent insights in the understanding of RA pathogenesis. In accordance with the complex nature of the disease, preclinical events extend over several sequential phases. In a genetically predisposed host, environmental factors will further increase susceptibility for incident RA. In the initial steps of preclinical disease, immune disturbance mechanisms take place outside the joint compartment, namely in mucosal surfaces, such as the lung, gums or gut. Herein, the persistent immunologic response to altered antigens will lead to breach of tolerance and trigger autoimmunity. In a second phase, the immune response matures and is amplified at a systemic level, with epitope spreading and widening of the autoantibody repertoire. Finally, the synovial and bone compartment are targeted by specific autoantibodies against modified antigens, initiating a local inflammatory response that will eventually culminate in clinically evident synovitis. In this review, we discuss the elaborate disease mechanisms in place during preclinical RA, providing a broad perspective in the light of current evidence.
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影响因子：
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作者：
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通讯作者：
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影响因子：
13.3
作者：
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影响因子：
27.4
作者：
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Satoh M
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影响因子：
16.6
作者：
Ai R;Hammaker D;Boyle DL;Morgan R;Walsh AM;Fan S;Firestein GS;Wang W
通讯作者：
Wang W
DOI：
10.3899/jrheum.091398
发表时间：
2010-09
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Arkema EV;Karlson EW;Costenbader KH
通讯作者：
Costenbader KH