Higley H, Persichitte K, Chu S, Waegell W, Vancheeswaran R, Black C
Celtrix Pharmaceuticals, Santa Clara, California.
Arthritis Rheum. 1994 Feb;37(2):278-88. doi: 10.1002/art.1780370218.
To determine the presence of transforming growth factor beta 1 (TGF beta 1) and inflammatory cell markers (HLA-DR and Factor XIIIa) and to compare these with the presence of type I procollagen, in clinically uninvolved and involved skin from patients with different subsets of systemic sclerosis (SSc), and to analyze circulating levels of TGF beta 1 in SSc patients.
TGF beta 1, HLA-DR, Factor XIIIa, and type I procollagen were detected in skin biopsy sections using a biotin-streptavidin-peroxidase system. Levels of circulating TGF beta 1 were measured using a capture enzyme-linked immunosorbent assay technique.
Patients with active diffuse cutaneous SSc (dcSSc) showed minimal TGF beta 1 but significant type I procollagen staining in involved skin, while the clinically uninvolved skin of these patients showed moderate extracellular and intra-epidermal TGF beta 1 immunoreactivity. Patients with limited cutaneous SSc (lcSSc) showed elevated TGF beta 1 staining in both involved and uninvolved skin, as well as procollagen staining. Significant TGF beta 1 reactivity, HLA-DR and Factor XIIIa immunoreactivity, numerous inflammatory cells, and procollagen staining were seen in specimens from patients with morphea. Sequential biopsies suggested the presence of cytokine activity at the earliest stages of disease, which was not maintained with progression of sclerosis. Among the disease groups studied, elevated levels of circulating TGF beta 1 were seen only in patients with morphea.
The pattern of TGF beta 1 staining in dermal sections from patients with dcSSc, lcSSc, and morphea suggests that this cytokine is important in the pathogenesis of scleroderma. Furthermore, the presence of TGF beta 1 prior to the onset of fibrosis indicates an early involvement of this growth factor, possibly in the inflammatory stage of the disease.
确定转化生长因子β1（TGFβ1）和炎症细胞标志物（HLA - DR和因子XIIIa）的存在，并将其与I型前胶原的存在情况进行比较；观察不同亚型系统性硬化症（SSc）患者临床未受累及受累皮肤的情况；分析SSc患者循环中TGFβ1的水平。
采用生物素 - 链霉亲和素 - 过氧化物酶系统检测皮肤活检切片中的TGFβ1、HLA - DR、因子XIIIa和I型前胶原。使用捕获酶联免疫吸附测定技术测量循环中TGFβ1的水平。
活动性弥漫性皮肤型SSc（dcSSc）患者受累皮肤中TGFβ1极少，但I型前胶原染色显著，而这些患者临床未受累皮肤显示中度细胞外及表皮内TGFβ1免疫反应性。局限性皮肤型SSc（lcSSc）患者受累及未受累皮肤中TGFβ1染色均升高，同时前胶原染色也升高。硬斑病患者的标本中可见显著的TGFβ1反应性、HLA - DR和因子XIIIa免疫反应性、大量炎症细胞及前胶原染色。连续活检表明在疾病最早阶段存在细胞因子活性，但随着硬化进展这种活性未持续存在。在所研究的疾病组中，仅硬斑病患者循环中TGFβ1水平升高。
dcSSc、lcSSc和硬斑病患者皮肤切片中TGFβ1染色模式表明该细胞因子在硬皮病发病机制中起重要作用。此外，在纤维化发生之前TGFβ1的存在表明该生长因子可能在疾病炎症阶段早期就已参与。
