Psoriasis is a chronic, immune-mediated inflammatory disease with heterogeneous manifestations. Reliable biomarkers reflecting disease severity and treatment response remain limited. Glycans-carbohydrate structures attached to proteins and lipids-play key roles in biological processes, contributing to functional specificity. Abnormal glycosylation has been implicated in the pathogenesis of inflammatory and neoplastic diseases, highlighting their potential as therapeutic targets and biomarkers. This study aimed to evaluate serum N-glycan profiles as potential biomarkers for psoriasis, focusing on the ratio of sialylated biantennary N-glycan (S) to fucosylated asialo-biantennary N-glycan (FA), termed the S/FA ratio. Serum samples from 45 patients with psoriasis, 12 with atopic dermatitis (AD), and 19 healthy controls were analyzed using high-performance liquid chromatography. The performance of the S/FA ratio was compared with reported biomarkers (CRP and CCL20), and its associations with Psoriasis Area and Severity Index (PASI) and treatment response were examined. The S/FA ratio was significantly higher in psoriasis than in healthy controls (p < 0.001) and correlated with PASI (r = 0.485, p < 0.001) and its components. Receiver operating characteristic analysis showed comparable diagnostic accuracy among the S/FA ratio (AUC = 0.788, sensitivity: 73.7%, specificity: 73.3%), CRP (AUC = 0.780), and CCL20 (AUC = 0.741). Changes in the S/FA ratio were correlated with improvements in PASI after systemic treatment (r = 0.467, p = 0.002), including a patients subgroup receiving IL-23 inhibitors. The S/FA ratio was not significantly influenced by demographics, comorbidities, or arthralgia. No significant difference was observed between psoriasis and AD, and the S/FA ratio was not significantly elevated in AD compared with healthy controls. The serum S/FA ratio may serve as a glycan-based biomarker associated with disease severity and treatment response in psoriasis, although its ability to distinguish psoriasis from other inflammatory diseases requires further validation in larger and treatment-naïve cohorts.
