Piera-Velazquez Sonsoles, Dillon Simon T, Gu Xuesong, Libermann Towia A, Jimenez Sergio A
Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Suite 509 BLSB, 233 S. 10th Street, Philadelphia, PA, 19107-5541, USA.
Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Arthritis Res Ther. 2025 Jul 10;27(1):146. doi: 10.1186/s13075-025-03595-8.
OBJECTIVE: A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics. METHODS: Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients with Diffuse SSc with SSc-ILD and 12 patients with Diffuse SSc without SSc-ILD. SOMAscan aptamer proteomics was performed with the first cohort and quantified the concentration levels of 1,305 proteins. Significant associations of differentially elevated or reduced proteins (p < 0.05 |FC|>1.2) discriminating between the two SSc clinical subsets were assessed. Validation of the results obtained from the proteomics analysis of the first cohort was performed with the second cohort. RESULTS: The aptamer proteomic analysis identified 29 proteins increased and 9 proteins decreased in SSc with SSc-ILD as compared to SSc without SSc-ILD. Principal component analysis using the 20 most significantly differentially expressed proteins resulted in excellent separation of the two SSc clinical subsets. Most of the differentially increased proteins converged around enhanced inflammatory responses, immune cell activation, cell death, and abnormal vascular functions and several of them displayed a highly significant correlation with the CO Diffusion Capacity Levels. CONCLUSION: Aptamer proteomic analysis of circulating exosomes from patients with Diffuse SSc with and without SSc-ILD identified several biologically plausible biomarkers that may be of value to differentiate these two SSc clinical subsets.
目的：系统性硬化症（SSc）临床管理中一个尚未满足的主要需求是缺乏经过充分验证的生物标志物用于早期诊断SSc相关间质性肺病（SSc-ILD）。本研究的目的是利用基于适配体的蛋白质组学方法，鉴定血清外泌体中可能作为潜在生物标志物的蛋白质，以区分无SSc-ILD的弥漫性SSc患者和伴有SSc-ILD的弥漫性SSc患者。 方法：从两组患者中分离血清外泌体。第一组包括15例无SSc-ILD的弥漫性SSc患者和14例伴有SSc-ILD的弥漫性SSc患者，第二组包括12例伴有SSc-ILD的弥漫性SSc患者和12例无SSc-ILD的弥漫性SSc患者。对第一组进行SOMAscan适配体蛋白质组学分析，定量检测1305种蛋白质的浓度水平。评估区分两个SSc临床亚组的差异升高或降低蛋白质（p < 0.05，|FC|>1.2）的显著相关性。用第二组对第一组蛋白质组学分析结果进行验证。 结果：与无SSc-ILD的SSc相比，适配体蛋白质组学分析确定在伴有SSc-ILD的SSc中有29种蛋白质增加，9种蛋白质减少。使用20种最显著差异表达的蛋白质进行主成分分析，可将两个SSc临床亚组很好地分离。大多数差异增加的蛋白质集中在增强的炎症反应、免疫细胞激活、细胞死亡和异常血管功能周围，其中几种与一氧化碳弥散能力水平高度相关。 结论：对伴有和不伴有SSc-ILD的弥漫性SSc患者的循环外泌体进行适配体蛋白质组学分析，鉴定出了几种生物学上合理的生物标志物，这些标志物可能有助于区分这两个SSc临床亚组。
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