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Background: This study conducted a comprehensive glycan analysis of serum to determine how glycan biomarkers are associated with the pathophysiology of chronic inflammatory demyelinating polyneuropathy (CIDP) and the effects of its treatment., Methods: We comparatively analyzed N- and O-glycans in the pretreatment serum of 27 treatment-naïve patients with typical CIDP and 20 age- and sex-matched healthy controls (HC) using mass spectrometry. We determined the association between clinical parameters and glycans. The serum glycan and neurofilament light-chain (NfL) levels were assessed at the baseline, and treatment response was defined according to the degree of improvement in the modified Rankin scale 12 weeks after the first dose of intravenous immunoglobulin (IVIg)., Results: Compared with the HC, the CIDP group demonstrated significantly lower levels of serum total N-glycans (CIDP, median 973.3 [IQR 836.2-1131.3] pmol/μL; HC, 1125.0 [1005.0-1236.2] pmol/μL; p < 0.05), especially sialylated N-glycans (CIDP, 898.0 [752.2-1037.2] pmol/μL; HC, 1064.4 [942.7-1189.8] pmol/μL; p < 0.01). In contrast, the O-glycan levels did not differ significantly between the two groups. The treatment response was associated with low N-glycan levels, but not with the serum NfL levels. Low levels of sialylated N-glycans were associated with resistance to treatment over 12 weeks, with an area under the curve of 0.822 (p < 0.01)., Conclusions: Low levels of sialylated N-glycans could potentially serve as a novel biomarker, reflecting pathophysiology and therapeutic resistance in typical CIDP., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)