White B
University of Maryland School of Medicine, Baltimore, USA.
Curr Opin Rheumatol. 1995 Nov;7(6):541-5. doi: 10.1097/00002281-199511000-00013.
Activation of both cellular and humoral immunity are early events in systemic sclerosis (SSc) that appear to contribute to disease pathogenesis. Recent reports suggest that CD4+ and CD8+ T cells and a subset of gamma delta T cells each may play a role in the disease. Interest in potential profibrotic effects of transforming growth factor-beta in SSc continues. Expression of a variety of adhesion molecules is increased on fibroblasts and endothelial cells in SSc patients, as are circulating levels of the same molecules. Different autoantibody specificities are generated in B cells from tight-skin mice by use of identical VH genes, with similar V kappa genes but different J kappa segments. Centromeric proteins, topoisomerase I, RNA polymerases I, II, and III, fibrillarin, and upstream binding factor may become autoantibody targets in SSc because they are presented to the immune system as part of larger multiunit complexes. Homology between target autoantigens and infectious agents suggests that molecular mimicry initiates some autoantibody responses in SSc patients. Genetic factors influence the pattern of autoantibodies produced in different populations. Exogenous agents can induce autoantibodies in humans and mice that are similar to those seen in spontaneous SSc.
细胞免疫和体液免疫的激活是系统性硬化症（SSc）早期出现的事件，似乎对疾病发病机制有影响。最近的报告表明，CD4 +和CD8 + T细胞以及γδT细胞亚群可能各自在该疾病中发挥作用。对转化生长因子-β在SSc中的潜在促纤维化作用的研究仍在继续。SSc患者的成纤维细胞和内皮细胞上多种粘附分子的表达增加，这些分子的循环水平也升高。通过使用相同的VH基因、相似的Vκ基因但不同的Jκ片段，在紧皮小鼠的B细胞中产生了不同的自身抗体特异性。着丝粒蛋白、拓扑异构酶I、RNA聚合酶I、II和III、核仁纤维蛋白以及上游结合因子可能成为SSc中的自身抗体靶点，因为它们作为较大多亚基复合物的一部分呈递给免疫系统。靶自身抗原与感染因子之间的同源性表明分子模拟引发了SSc患者的一些自身抗体反应。遗传因素影响不同人群中产生的自身抗体模式。外源性因素可在人和小鼠中诱导出与自发性SSc中所见相似的自身抗体。
