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Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS)
Rheumatology ( IF 4.7 ) Pub Date : 2024-12-19 , DOI: 10.1093/rheumatology/keae698
Rebecca L Ross, Begoña Caballero-Ruiz, Emily L Clarke, Vishal Kakkar, Christopher W Wasson, Panji Mulipa, Enrico De Lorenzis, Will Merchant, Stefano Di Donato, Andrea Rindone, Ariane L Herrick, Christopher P Denton, Natalia A Riobo-Del Galdo, Francesco Del Galdo

Objective The Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR study showed that, despite not showing any clinical sign of disease, patients with Raynaud’s and antinuclear antibodies and/or capillaroscopy abnormalities often progress to systemic sclerosis (SSc) within 5 years. We aimed to determine whether VEDOSS biosamples show biological SSc activity pre-clinically. Methods Skin biopsies were histologically analysed. Dermal fibroblasts analysed by RT-qPCR and gel contraction assays. Sera were assayed by Luminex (CXCL10) or ELISA (ELF score). Healthy controls (HC) and SSc biosamples were used for controls. Results Overall, 114 consecutive VEDOSS patients were enrolled, of which 36 consented to have skin biopsies. Skin biopsies showed a variable but overall increased collagen staining and skin thickness, increased perivascular infiltrate of CD45 positive cells and CXCL10 expression. In vitro, VEDOSS dermal fibroblasts showed increased profibrotic gene expression and contractibility compared with HC. Increased serological CXCL10 (mean [SD]; 75.90 [107.80] vs HC 39.90 [26.27] pg/ml, p = 0.02) and ELF score was evident in VEDOSS compared with HC (8.19 [0.78] vs 8.55 [0.79], p = 0.04). In longitudinal analysis of a median of 27.5 (IQR 44.5) months, 14.9% of VEDOSS patients progressed to SSc. Baseline CXCL10 serum concentration was significantly higher in the VEDOSS patients that progressed (2-fold increase, p = 0.0071) and correlated with ELF score (R = 0.3096, p = 0.0065). Conclusions Despite not fulfilling classification criteria, VEDOSS patients show SSc-linked fibrosis and immunity dysregulation both within the tissue and sera, supporting a biological diagnosis of disease and a window of opportunity to detect the biological pathways amenable for preventive intervention.

中文翻译:


系统性硬化症的生物学标志存在于 SSc 极早期诊断 (VEDOSS) 患者的皮肤和血清中



目的 系统性硬化症的极早期诊断 (VEDOSS) EUSTAR 研究表明,尽管没有表现出任何疾病的临床体征,但具有雷诺氏抗体和/或抗核抗体和/或毛细血管镜检查异常的患者通常会在 5 年内发展为系统性硬化症 (SSc)。我们旨在确定 VEDOSS 生物样品是否在临床前显示生物 SSc 活性。方法 对皮肤活检进行组织学分析。通过 RT-qPCR 和凝胶收缩测定分析真皮成纤维细胞。通过 Luminex (CXCL10) 或 ELISA (ELF 评分) 检测血清。健康对照 (HC) 和 SSc 生物样品用于对照。结果 共连续入组 114 例 VEDOSS 患者,其中 36 例同意进行皮肤活检。皮肤活检显示可变但总体上胶原蛋白染色和皮肤厚度增加,CD45 阳性细胞的血管周围浸润增加和 CXCL10 表达增加。在体外,与 HC 相比,VEDOSS 真皮成纤维细胞显示出促纤维化基因表达和收缩性增加。与 HC 相比,VEDOSS 的血清学 CXCL10 (平均值 [SD];75.90 [107.80] vs HC 39.90 [26.27] pg/ml,p = 0.02)和 ELF 评分增加明显 (8.19 [0.78] vs 8.55 [0.79],p = 0.04)。在中位 27.5 (IQR 44.5) 个月的纵向分析中,14.9% 的 VEDOSS 患者进展为 SSc。进展的 VEDOSS 患者的基线 CXCL10 血清浓度显着升高 (增加 2 倍,p = 0.0071) 并与 ELF 评分相关 (R = 0.3096,p = 0.0065)。 结论 尽管不符合分类标准,但 VEDOSS 患者在组织和血清内均表现出 SSc 连锁纤维化和免疫失调,支持疾病的生物学诊断和检测适合预防性干预的生物途径的机会之窗。
更新日期:2024-12-19
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