Zhu Mengya, Mao Xinliang, Huang Xianqian, Gan Minzhi, Zhang Keyue, Chen Yong
Department of Rheumatology and Immunology, Ningbo No.2 hospital, Ningbo, China.
Emergency Department, Ningbo No.2 hospital, Ningbo, China.
Immunol Invest. 2025 Jan;54(1):1-17. doi: 10.1080/08820139.2024.2410743. Epub 2024 Oct 2.
Behcet's disease (BD) is a rare and recurrent autoinflammatory disorder characterized by systemic vasculitis, frequently manifested as recurrent aphthous stomatitis (RAS). We aim to identify specific serum proteins to discriminate between BD and idiopathicRAS.
Peripheral blood was collected from 12 BD patients, 12 idiopathic RAS patients, and 21 healthy volunteers. The serum samples underwent Tandem Mass Tag-based mass spectrometry analysis. Differentially expressed proteins (DEPs) were identified for KEGG pathway enrichment, Gene Ontology (GO), and protein-protein interaction (PPI) analyses. ELISA was utilized to verify two BD-specific DEPs in another cohort consisting of 18 BD patients, 18 idiopathic RAS patients, and 18 controls.
Compared with RAS serum, BD serum showed 242 DEPs. 49 proteins were differentially expressed in BD but not RAS serum compared to healthy controls. KEGG pathway and GO analyses revealed that DEPs in BD and RAS have similar biological functions and cellular distributions, featuring a significant association with pathways regulating blood coagulation and immune response. When comparing DEPs between BD and RAS, several keratins emerged as markers that distinguish RAS from BD. We also identified multiple DEPs in BD but not RAS patients. PPI analysis uncovered that lipoprotein metabolism regulators serve as hub proteins, indicating their potentially essential roles in BD pathology. In addition, ELISA results confirmed the elevated LRG1 and SOD3 levels in BD, but not RAS patients, compared to healthy donors.
Our data uncovered novel serum proteins that distinguish BD from RAS, which may potentially be useful in BD diagnosis and treatment.
白塞病（BD）是一种罕见的复发性自身炎症性疾病，其特征为系统性血管炎，常表现为复发性阿弗他口炎（RAS）。我们旨在鉴定出可区分BD和特发性RAS的特定血清蛋白。
采集了12例BD患者、12例特发性RAS患者和21名健康志愿者的外周血。血清样本进行了基于串联质量标签的质谱分析。鉴定出差异表达蛋白（DEPs），用于KEGG通路富集分析、基因本体（GO）分析和蛋白质-蛋白质相互作用（PPI）分析。在另一个由18例BD患者、18例特发性RAS患者和18名对照组成的队列中，利用酶联免疫吸附测定（ELISA）来验证两种BD特异性DEPs。
与RAS血清相比，BD血清显示出242种DEPs。与健康对照相比，有49种蛋白质在BD血清中差异表达，而在RAS血清中未差异表达。KEGG通路和GO分析显示，BD和RAS中的DEPs具有相似的生物学功能和细胞分布，与调节凝血和免疫反应的通路显著相关。在比较BD和RAS之间的DEPs时，几种角蛋白成为区分RAS和BD的标志物。我们还在BD患者而非RAS患者中鉴定出多种DEPs。PPI分析发现脂蛋白代谢调节因子作为枢纽蛋白，表明它们在BD病理中可能具有重要作用。此外，ELISA结果证实，与健康供体相比，BD患者而非RAS患者的富含亮氨酸α2糖蛋白1（LRG1）和超氧化物歧化酶3（SOD3）水平升高。
我们的数据揭示了可区分BD和RAS的新型血清蛋白，这可能对BD的诊断和治疗有潜在帮助。
