Plasma IgG glycosylation profiling reveals the biological features of early COPD

Chronic inflammatory and immune dysregulation are critical drivers in the development and progression of chronic obstructive pulmonary disease (COPD). Posttranslational modifications, such as glycosylation of Immunoglobulin G (IgG), modulates systemic inflammatory homeostasis. This study aims to profile plasma IgG glycopeptides (IgGPs) in COPD patients to uncover new insights into its pathogenesis and to identify novel biomarkers. Plasma IgG N-glycopeptides from 90 COPD patients, 45 clinical defined early COPD (CECOPD) patients and 90 healthy individuals were analyzed using an integrated platform that combines Fe3O4@PDA@DETA nanospheres enrichment with high-resolution mass spectrometry measurement. Correlations between IgG N-glycoforms and clinical parameters were assessed to explore underlying mechanisms of COPD progression. Disease-specific IgGPs were identified in both ECOPD and COPD cohorts. Notably, IgG glyco-pattern, rather than IgG levels, changed with disease progression. Early COPD patients showed decreased bisection and increased site-specific afucosylated galactosylation and fucosylation of IgG, indicating an anti-inflammatory state. In contrast, COPD patients gave increased inflammation, characterized by reduced galactosylation and sialylation. Interestingly, a subset of healthy controls displayed IgGPs patterns similar to early COPD, possibly reflecting the impact of substantial smoking exposure and associated immune responses. These findings suggest that plasma IgG glycosylation could serve as a potential biomarker for early COPD diagnosis, providing valuable insights into immune system changes during disease progression.