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.