Sakkas Lazaros I, Chikanza Ian C, Platsoucas Chris D
Rheumatology Section, Thessaly University School of Medicine, 22 Papakyriazi Street, Larisa 41222, Greece.
Nat Clin Pract Rheumatol. 2006 Dec;2(12):679-85. doi: 10.1038/ncprheum0346.
Systemic sclerosis is characterized by extensive fibrosis, microvascular stenosis and autoantibody production. All three characteristics can be accounted for by activation of cells of the immune system. Activation of T cells is antigen-driven and occurs early in the course of the disease, before microscopic evidence of fibrosis. Activated T cells are predominantly of the type 2 T-helper lineage, and produce interleukin-4 and interleukin-13, which induce fibrosis. B cells are also activated early in the course of the disease and, through the production of autoantibodies, cause fibroblasts to adopt a profibrotic phenotype. Macrophages in perivascular infiltrates are activated and produce CC-chemokine ligand 2, transforming growth factor beta and platelet derived growth factor, all of which promote fibrosis and fibroproliferation. These new insights have direct impact on the treatment of patients with systemic sclerosis; therapies that target T cells, B cells and their harmful mediators are a logical approach, and preliminary data are promising.
系统性硬化症的特征是广泛纤维化、微血管狭窄和自身抗体产生。这三个特征都可归因于免疫系统细胞的激活。T细胞的激活是抗原驱动的，且在疾病进程早期、纤维化的微观证据出现之前就已发生。活化的T细胞主要是2型辅助性T细胞谱系，可产生诱导纤维化的白细胞介素-4和白细胞介素-13。B细胞在疾病进程早期也被激活，并通过产生自身抗体使成纤维细胞呈现促纤维化表型。血管周围浸润中的巨噬细胞被激活，并产生CC趋化因子配体2、转化生长因子β和血小板衍生生长因子，所有这些都促进纤维化和纤维增殖。这些新见解对系统性硬化症患者的治疗有直接影响；针对T细胞、B细胞及其有害介质的疗法是一种合理的方法，初步数据很有前景。
