The University of Texas Health Science Center at Houston and McGovern Medical School, Houston, and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
The University of Texas Health Science Center at Houston and McGovern Medical School, Houston.
Arthritis Rheumatol. 2021 Apr;73(4):660-670. doi: 10.1002/art.41570. Epub 2021 Feb 28.
To provide a large-scale assessment of serum protein dysregulation in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features.
We investigated serum protein profiles of 66 participants with dcSSc at baseline who were enrolled in the Scleroderma: Cyclophosphamide or Transplant Trial and 66 age- and sex-matched healthy control subjects. A panel of 230 proteins, including several cytokines and chemokines, was investigated. Whole blood gene expression profiling in concomitantly collected samples was performed.
Among the participants with dcSSc, the mean disease duration was 2.3 years. All had interstitial lung disease (ILD), and none were being treated with immunosuppressive agents at baseline. Ninety proteins were differentially expressed in participants with dcSSc compared to healthy control subjects. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion, and diapedesis were the top overrepresented pathways. Eighteen proteins correlated with the modified Rodnan skin thickness score (MRSS). Soluble epidermal growth factor receptor was significantly down-regulated in dcSSc and showed the strongest negative correlation with the MRSS, being predictive of the score's course over time, whereas α -antichymotrypsin was significantly up-regulated in dcSSc and showed the strongest positive correlation with the MRSS. Furthermore, higher levels of cancer antigen 15-3 correlated with more severe ILD, based on findings of reduced forced vital capacity and higher scores of disease activity on high-resolution computed tomography. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses.
Diffuse cutaneous SSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells.
大规模评估弥漫性皮肤系统性硬化症（dcSSc）中的血清蛋白失调，并研究与 SSc 纤维化特征相关的血清蛋白。
我们研究了 66 名基线时患有 dcSSc 的参与者的血清蛋白谱，这些参与者参加了硬皮病：环磷酰胺或移植试验，并与 66 名年龄和性别匹配的健康对照者进行了比较。研究了包括几种细胞因子和趋化因子在内的 230 种蛋白质的蛋白质谱。同时采集的样本进行全血基因表达谱分析。
在 dcSSc 参与者中，平均疾病持续时间为 2.3 年。所有参与者均患有间质性肺病（ILD），且在基线时均未接受免疫抑制治疗。与健康对照组相比，90 种蛋白质在 dcSSc 参与者中表达差异。与之前的整体皮肤转录结果相似，肝纤维化、粒细胞和无粒细胞黏附以及出芽是最被过度代表的途径。有 18 种蛋白质与改良的罗德曼皮肤厚度评分（MRSS）相关。可溶性表皮生长因子受体在 dcSSc 中显著下调，与 MRSS 呈最强负相关，可预测评分随时间的变化，而α-抗糜蛋白酶在 dcSSc 中显著上调，与 MRSS 呈最强正相关。此外，更高水平的癌抗原 15-3 与更严重的 ILD 相关，这基于发现肺活量降低和高分辨率计算机断层扫描的疾病活动评分更高。只有 14 个基因在血清蛋白和全血 RNA 基因表达分析中表现出相同方向的显著差异表达。
弥漫性皮肤 SSc 具有明显的血清蛋白谱，与纤维化和免疫细胞黏附和出芽相关的蛋白质明显失调。大多数 SSc 血清蛋白的差异表达可能起源于外周血细胞之外。
