Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
Rheumatology and Clinical Immunology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy.
Front Immunol. 2023 Sep 11;14:1246777. doi: 10.3389/fimmu.2023.1246777. eCollection 2023.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease that affects multiple organs, leading to elevated morbidity and mortality with limited treatment options. The early detection of organ involvement is challenging as there is currently no serum marker available to predict the progression of SSc. The aptamer technology proteomic analysis holds the potential to correlate SSc manifestations with serum proteins up to femtomolar concentrations.
This is a two-tier study of serum samples from women with SSc (including patients with interstitial lung disease - ILD - at high-resolution CT scan) and age-matched healthy controls (HC) that were first analyzed with aptamer-based proteomic analysis for over 1300 proteins. Proposed associated proteins were validated by ELISA first in an independent cohort of patients with SSc and HC, and selected proteins subject to further validation in two additional cohorts.
The preliminary aptamer-based proteomic analysis identified 33 proteins with significantly different concentrations in SSc compared to HC sera and 9 associated with SSc-ILD, including proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, leukocyte recruitment, activation, and signaling. Further validations in independent cohorts ultimately confirmed the association of specific proteins with early SSc onset, specific organ involvement, and serum autoantibodies.
Our multi-tier proteomic analysis identified serum proteins discriminating patients with SSc and HC or associated with different SSc subsets, disease duration, and manifestations, including ILD, skin involvement, esophageal disease, and autoantibodies.
系统性硬化症（SSc）是一种自身免疫性结缔组织疾病，可影响多个器官，导致发病率和死亡率升高，且治疗选择有限。由于目前尚无血清标志物可预测 SSc 的进展，因此早期发现器官受累具有挑战性。适体技术蛋白质组学分析有可能将 SSc 表现与血清蛋白相关联，达到飞摩尔浓度。
这是一项对 SSc 女性（包括高分辨率 CT 扫描显示间质性肺病 -ILD- 的患者）和年龄匹配的健康对照者（HC）的血清样本进行的两阶段研究，首先采用基于适体的蛋白质组学分析对超过 1300 种蛋白质进行分析。候选相关蛋白首先在独立的 SSc 患者和 HC 队列中通过 ELISA 进行验证，然后选择进一步在另外两个队列中进行验证的蛋白。
初步的基于适体的蛋白质组学分析确定了 33 种在 SSc 血清中与 HC 血清相比浓度显著不同的蛋白，其中 9 种与 SSc-ILD 相关，包括参与细胞外基质形成和细胞-细胞黏附、血管生成、白细胞募集、激活和信号转导的蛋白。在独立队列中的进一步验证最终证实了特定蛋白与早期 SSc 发病、特定器官受累和血清自身抗体相关。
我们的多层面蛋白质组学分析鉴定了区分 SSc 患者和 HC 或与不同 SSc 亚型、疾病持续时间和表现相关的血清蛋白，包括ILD、皮肤受累、食管疾病和自身抗体。
