Nihtyanova Svetlana I, Denton Christopher P
Centre for Rheumatology and Connective Tissue Diseases, University College London, London, UK.
J Scleroderma Relat Disord. 2020 Mar;5(2 Suppl):6-16. doi: 10.1177/2397198320903867. Epub 2020 Mar 5.
Systemic sclerosis is an autoimmune disease leading to vasculopathy and fibrosis of skin and internal organs. Despite likely shared pathogenic mechanisms, the patterns of skin and lung fibrosis differ. Pathogenesis of interstitial lung disease, a major cause of death in systemic sclerosis, reflects the intrinsic disease pathobiology and is associated with distinct clinical phenotypes and laboratory characteristics. The commonest histological pattern of systemic sclerosis-interstitial lung disease is non-specific interstitial pneumonia. Systemic sclerosis-interstitial lung disease pathogenesis involves multiple components, including susceptibility and triggering factors, which could be genetic or environmental. The process is amplified likely through ongoing inflammation and the link between inflammatory activity and fibrosis with IL6 emerging as a key mediator. The disease is driven by epithelial injury, reflected by markers in the serum, such as surfactant proteins and KL-6. In addition, mediators that are produced by epithelial cells and that regulate inflammatory cell trafficking may be important, especially CCL2. Other factors, such as CXCL4 and CCL18, point towards immune-mediated damage or injury response. Monocytes and alternatively activated macrophages appear to be important. Transforming growth factor beta appears central to pathogenesis and regulates epithelial repair and fibroblast activation. Understanding pathogenesis may help to unravel the stages of systemic sclerosis-interstitial lung disease, risks of progression and determinants of outcome. With this article, we set out to review the multiple factors, including genetic, environmental, cellular and molecular, that may be involved in the pathogenesis of systemic sclerosis-interstitial lung disease and the mechanisms leading to sustained fibrosis. We propose a model for the pathogenesis of systemic sclerosis-interstitial lung disease, based on the available literature.
系统性硬化症是一种自身免疫性疾病，可导致血管病变以及皮肤和内脏器官的纤维化。尽管可能存在共同的致病机制，但皮肤和肺部纤维化的模式有所不同。间质性肺病是系统性硬化症的主要死因，其发病机制反映了内在的疾病病理生物学，并与不同的临床表型和实验室特征相关。系统性硬化症 - 间质性肺病最常见的组织学模式是非特异性间质性肺炎。系统性硬化症 - 间质性肺病的发病机制涉及多个组成部分，包括易感性和触发因素，这些因素可能是遗传的或环境的。该过程可能通过持续的炎症以及炎症活动与纤维化之间的联系而被放大，其中白细胞介素6成为关键介质。该疾病由上皮损伤驱动，血清中的标志物如表面活性蛋白和KL - 6可反映这一点。此外，由上皮细胞产生并调节炎症细胞迁移的介质可能很重要，尤其是趋化因子CCL2。其他因素，如CXCL4和CCL18，表明存在免疫介导的损伤或损伤反应。单核细胞和交替激活的巨噬细胞似乎很重要。转化生长因子β似乎在发病机制中起核心作用，并调节上皮修复和成纤维细胞活化。了解发病机制可能有助于阐明系统性硬化症 - 间质性肺病的阶段、进展风险和预后决定因素。在本文中，我们着手综述可能参与系统性硬化症 - 间质性肺病发病机制以及导致持续性纤维化的机制的多种因素，包括遗传、环境、细胞和分子因素。我们根据现有文献提出了一种系统性硬化症 - 间质性肺病的发病机制模型。
