Therapeutic targets in systemic sclerosis 英文参考文献.docVIP

Available online /content/9/S2/S6 Review Therapeutic targets in systemic sclerosis Christopher P Denton Centre for Rheumatology, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF, UK Corresponding author: Christopher P Denton, c.denton@medsch.ucl.ac.uk Published: 15 August 2007 Arthritis Research Therapy 2007, 9(Suppl 2):S6 (doi:10.1186/ar2190) This article is online at /content/9/S2/S6 ? 2007 BioMed Central Ltd Abstract hallmark feature of SSc skin. As the disease progresses there is evidence of a profibrotic fibroblastic cell population becoming established within the skin. This leads to increased extracellular matrix deposition. Early studies showed that these profibrotic cells are initially located around blood vessels but that later they are more generally distributed. As the disease becomes well established lesional skin becomes relatively avascular, and after 12 to 18 months there is often little evidence of ongoing inflammation. This suggests that there are probably distinct phases, at least in the skin, when the component processes of SSc might be amenable to therapeutic modulation [1]. Thus, targeted therapy is likely to depend critically on disease stage and subset. The precise aetiology of systemic sclerosis (SSc) remains elusive, but significant advances over the past few years have improved our understanding of the underlying pathogenic processes and pathways and mediators that are potential identified key therapeutic targets. The situation is complicated by the clinical heterogeneity of SSc and the differential pathogenesis that underlies the two commonest subsets, namely diffuse and limited cutaneous disease. However, there are common mediators that could be targeted to provide clinical benefit in both types of disease. To date, clinical success with therapies