Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

Abstract

Background Glycosylation plays a crucial role in various pathologic conditions, including inflammation. 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 analyzedN- andO-glycans in the pretreatment serum of 27 treatment-naïve patients with typical CIDP and age- and sex-matched 20 healthy controls (HC) using mass spectrometry. We determined the association between clinical parameters and glycans. Treatment response was defined according to the degree of improvement in the modified Rankin Scale 2 weeks after the first dose of intravenous immunoglobulin (IVIg), and the serum glycan and neurofilament light chain (NfL) levels were assessed at the baseline. Results Compared with the HC, the CIDP group demonstrated significantly lower levels of serum totalN–glycans (CIDP, median 973.3 [IQR 836.2-1131.3] pmol/µĹ; HC, 1125.0 [1005.0-1236.2] pmol/µĹ; p < 0.05), especially sialylatedN–glycans (CIDP, 898.0 [752.2-1037.2] pmol/µĹ; HC, 1064.4 [942.7-1189.8] pmol/µĹ; p < 0.01). In contrast, theO–glycan levels did not differ significantly between the two groups. Treatment response was associated with lowN–glycan levels but not with the serum NfL levels. For individual glycans, low levels of Hex2HexNAc2NeuAc2 [α2,6/α2,6] + Man3GlcNAc2, α2,6-linked sialylatedN–glycans, showed the treatment response group to have an area under the curve of 0.802 (p < 0.05).