Plasma IgGGlycosylation Profiling Reveals the BiologicalFeatures of Early Chronic Obstructive Pulmonary Disease

Chronic inflammatory and immune dysregulation are critical drivers of the development and progression of chronic obstructive pulmonary disease (COPD). Posttranslational modifications, such as glycosylation of Immunoglobulin G (IgG), are crucial in modulating systemic inflammatory homeostasis. This study aims to profile plasma IgG glycopeptides (IgGPs) in COPD patients to uncover new insights into their pathogenesis and to identify novel biomarkers. An integrated platform that combines Fe₃O₄@PDA@DETA nanospheres enrichment with high-resolution mass spectrometry measurement was employed to analyze plasma IgG N-glycopeptides from 90 COPD patients, 45 clinically defined early COPD (CECOPD) patients, and 90 healthy individuals. To explore the underlying mechanism of COPD progression, correlations between IgG N-glycoforms and clinical parameters were assessed. Disease-specific IgGPs were identified in both the ECOPD and COPD cohorts. Notably, it was the IgG glycopattern, rather than the IgG levels themselves, that underwent changes as the disease progressed. In early COPD patients, there was a decrease in bisection, accompanied by an increase in site-specific afucosylated galactosylation and fucosylation of IgG, indicating an anti-inflammatory state. Conversely, in COPD patients, an increase in inflammation was observed, which was characterized by reduced galactosylation and sialylation. Interestingly, a subset of healthy controls displayed IgGP patterns similar to those of early COPD, possibly reflecting the impact of smoking and the associated immune responses. We finally identified 6 anti-inflammatory and 2 pro-inflammatory IgGPs as ECOPD-specific IgGP indicators. Collectively, these findings suggest that plasma IgG glycosylation holds great potential as a biomarker for early COPD diagnosis, providing valuable insights into the immune system changes during disease progression. The raw data files are publicly accessible via the ProteomeXchange Consortium with the identifier PXD056374.