Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

Glycomics is a new subspecialty in omics systems sciences that offers significant promise for next-generation biomarkers on disease susceptibility, drug target discovery, and precision medicine. In this context, alternative immunoglobulin G (IgG) N-glycosylation has been reportedly implicated in several common chronic diseases, although systematic assessment is currently lacking in the literature. We conducted a systematic review of observational studies on IgG N-glycan variability and susceptibility to common chronic diseases. Observational studies reporting an association between diseases (such as colorectal cancer, dyslipidemia, ischemic stroke, rheumatoid arthritis, and systemic lupus erythematosus) and IgG N-glycans quantified by ultraperformance liquid chromatography were included. The glycans were categorized into 24 initial IgG glycan peaks (GPs). Notably, aging positively correlated with GP1, GP2, GP4-7, GP10, GP11, GP19, and GP24, while negatively correlated with GP8, GP12-15, GP17, GP18, GP20, GP21, and GP23 (p < 0.05). The absolute value of significant correlation coefficients of age and IgG glycans ranged from 0.043 to 0.645. We found that the high levels of GP1-4, GP6, GP7, and GP24 and low levels of GP9, GP13-15, GP18, and GP23 could potentially increase the risk of disease. In conclusion, the present systematic review suggests that the field of glycomics, and GP1-4, GP6, GP7, GP9, GP13-15, GP18, GP23, and GP24 in particular, holds promise for further candidate biomarker research on susceptibility to common chronic diseases.