Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Experimental and Clinical Medicine, Division of Rheumatology, Careggi University Hospital, University of Florence, Florence, Italy.
Rheumatology (Oxford). 2022 Jul 6;61(7):2770-2782. doi: 10.1093/rheumatology/keab859.
SSc is a chronic autoimmune rheumatic disease that involves numerous organs and presents major management challenges. The histopathologic hallmarks of SSc include vasculopathy, fibrosis and autoimmune phenomena involving both innate and adaptive immune systems. Purinergic signalling is a pathway that may be implicated in the pathophysiology of several of these disease manifestations. Extracellular purines are potent signalling mediators, which have been shown to be dysregulated in SSc. As examples, purines can exacerbate vasculopathy and provoke platelet dysfunction; as well as contributing to immune dysregulation. Elements of purinergic signalling further promote organ and tissue fibrosis in several disease models. Here, we provide an overview of extracellular purine metabolism in purinergic signalling and link disorders of these to the molecular pathology of SSc. We also discuss targeting the purinergic signalling and explore the translational applications for new therapeutic options in SSc.
系统性硬化症是一种慢性自身免疫性风湿病，涉及多个器官，存在重大管理挑战。系统性硬化症的组织病理学特征包括血管病变、纤维化和涉及固有和适应性免疫系统的自身免疫现象。嘌呤能信号是一种可能与多种疾病表现的病理生理学有关的途径。细胞外嘌呤是有效的信号介质，已显示在系统性硬化症中失调。例如，嘌呤可以加重血管病变并引发血小板功能障碍；并有助于免疫失调。嘌呤能信号的元素进一步促进几种疾病模型中的器官和组织纤维化。在这里，我们提供嘌呤能信号中外源嘌呤代谢的概述，并将这些紊乱与系统性硬化症的分子病理学联系起来。我们还讨论了靶向嘌呤能信号，并探讨了系统性硬化症中新治疗选择的转化应用。
