Relationship between autoimmunity and COPD: an investigation based on proteomic profiling and antinuclear antibody screening

Chronic Obstructive Pulmonary Disease is a major global health concern with significant morbidity and mortality, characterized by heterogeneity influenced by inflammation, oxidative stress, and autoimmunity. This study investigated the role of autoimmunity in stable and exacerbated COPD phenotypes using proteomic and immunological analyses to elucidate molecular mechanisms and identify potential biomarkers. Plasma samples from COPD phenotypes and healthy controls were analyzed using label-free mass spectrometry to identify differentially expressed proteins. Functional annotation and pathway enrichment analysis highlighted proteins linked to autoimmunity, while immunological assays assessed anti-nuclear antibody prevalence and intensity using ANA ELISA and indirect immunofluorescence. The study identified differentially expressed proteins, namely, DNA repair protein XRCC2, phosphatidyl inositol glycan-specific phospholipase D, E3 ubiquitin protein ligase SHPRH, and Protocadherin-β, implicated in autoimmune pathways. Pathway enrichment analysis of these proteins highlighted the uPAR-mediated signaling, mTOR, PI3K/Akt, ARF6, and S1P signaling pathways, known for their roles in autoimmunity. Immunological assays revealed ANA positivity in 47% of stable COPD and 36% of exacerbated COPD, among which, 80% exhibited a speckled fluorescence pattern, often associated with anti-SSA and anti-SSB antibodies. The findings highlight the potential role of autoimmunity in COPD pathogenesis, suggesting phenotype-specific immune dysregulation, providing a basis for future biomarker and therapeutic research.

慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease，COPD）是全球性重大公共健康问题，伴随显著的发病率与死亡率，其异质性受炎症、氧化应激及自身免疫过程共同调控。本研究借助蛋白质组学与免疫学分析手段，探究自身免疫在稳定型与急性加重型COPD表型中的作用，以期阐明其分子机制并筛选潜在生物标志物。研究采用无标记质谱技术，对不同表型COPD患者及健康对照者的血浆样本进行检测，以鉴定差异表达蛋白。通过功能注释与通路富集分析，本研究锁定了与自身免疫通路相关的差异蛋白；同时采用抗核抗体（Anti-nuclear Antibody，ANA）酶联免疫吸附试验（Enzyme-Linked Immunosorbent Assay，ELISA）与间接免疫荧光法，评估抗核抗体的阳性率与表达强度。本研究共鉴定出数种与自身免疫通路密切相关的差异表达蛋白，具体包括DNA修复蛋白XRCC2、磷脂酰肌醇聚糖特异性磷脂酶D、E3泛素蛋白连接酶SHPRH以及原钙粘蛋白-β（Protocadherin-β）。对上述蛋白的通路富集分析显示，其显著富集于尿激酶型纤溶酶原激活物受体（urokinase-type plasminogen activator receptor, uPAR）介导的信号通路、雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）、PI3K/Akt、ARF6以及1-磷酸鞘氨醇（Sphingosine-1-phosphate, S1P）信号通路，上述通路均已被证实与自身免疫过程相关。免疫学检测结果显示，稳定型COPD患者中47%呈ANA阳性，急性加重型COPD患者中该阳性率为36%；其中80%的阳性样本呈现斑点状荧光模式，该模式通常与抗SSA及抗SSB抗体相关。本研究结果证实了自身免疫在COPD发病机制中的潜在作用，提示存在表型特异性的免疫失调，为后续生物标志物开发与治疗靶点研究提供了重要理论依据。