系统性硬化症(SSc)是一种罕见但致命的疾病，其特征为自身免疫反应、血管病变和纤维化。与SSc相关的纤维化并发症与严重的发病率和死亡率相关。以前的SSc研究确定纤维母细胞是纤维化的主要推动因素，然而，促进其发展的机制尚不清楚。异常糖基化，特别是多巴山羊膜素(polySia)，已被描述为侵袭性癌症的突出特征。受此观察的启发，我们旨在确定polySia在多种形式的SSc中是否发生失调。所有SSc患者均符合2013年ACR/EULAR标准。患者分为局限型皮肤型(SSc，N = 5或皮肤或血清中的polySia定量的46名患者)，弥漫型皮肤型(SSc，N = 11或皮肤或血清中的polySia定量的18名患者)或接受自体干细胞移植(SSc，N = 4)的弥漫型皮肤患者(术后)。通过免疫荧光显微镜法测量了10μm皮肤切片中的皮肤polySia水平，在每个群组(健康志愿者(HC)、SSc、术后-ASCT)中进行了定量，并与皮肤纤维化(通过修正的Rodnan皮肤评分(mRSS))进行了相关分析。类似地，血清polySia在每个群组中进行了定量，并与mRSS的严重程度相关。皮肤polySia水平在SSc患者中最高(HC<0.001)，与所有群组中的纤维化程度相关(P=0.008)。所有SSc群组的血清polySia水平较高(p<0.001)，与mRSS的严重程度相关(p<0.0001)。多巴山羊膜素在SSc患者的皮肤和血清中更丰富，并与皮肤纤维化程度相关。多巴山羊膜素的异常表达凸显了其在进展性SSc患者中作为生物标记物的潜力。SSc中失调的多巴山羊膜素水平进一步强调了SSc中类似癌症的表型，可能促进纤维化和免疫失调。版权所有©2023。由Elsevier Ltd.出版。

Systemic sclerosis (SSc) is a rare but deadly disease characterized by autoimmunity, vasculopathy, and fibrosis. Fibrotic complications associated with SSc correlate with severe morbidity and mortality. Previous studies in SSc have identified fibroblasts as the primary drivers of fibrosis; however, the mechanism(s) promoting this are not well understood. Aberrant glycosylation, particularly polysialylation (polySia), has been described as a prominent feature of aggressive cancers. Inspired by this observation, we aimed to determine if polySia is dysregulated in various forms of SSc.All patients with SSc met the 2013 ACR/EULAR. Patients were sub-classified into limited cutaneous (lSSc, N = 5 or 46 patients for polySia quantification in the dermis or serum; respectively), diffuse cutaneous (dSSc, N = 11 or 18 patients for polySia quantification in the dermis or serum; respectively), or patients with dSSc treated with an autologous stem cell transplantation (post-ASCT, N = 4 patients for quantification in the dermis). Dermal polySia levels were measured via immunofluorescence microscopy in 10 μm dermal sections, quantified in each group (healthy volunteers (HC), lSSc, dSSc, and post-ASCT) and correlated with skin fibrosis (via the modified Rodnan skin score (mRSS)). Similarly, serum polySia was quantified in each group, and correlated with the mRSS.Dermal polySia levels were highest in patients with dSSc (compared to HC < 0.001), and correlated with the degree of fibrosis in all of the groups (P = 0.008). Serum polySia was higher in all SSc groups (p < 0.001) and correlated with the severity of mRSS (p < 0.0001).Polysia is more abundant in the skin and sera from patients with SSc and correlates with the degree of skin fibrosis. The aberrant expression of polySia highlights its potential use as a biomarker in patients with progressive forms of SSc. Dysregulated polySia levels in SSc further emphasizes the cancer-like phenotype present in SSc, which may promote fibrosis and immune dysregulation.Copyright © 2023. Published by Elsevier Ltd.