Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Furukawa Soma , Fukami Yuki , Hanamatsu Hisatoshi , Yokota Ikuko , Furukawa Jun-ichi , Hane Masaya , Kitajima Ken , Sato Chihiro , Hiraga Keita , Satake Yuki , Yagi Satoru , Koike Haruki , Katsuno Masahisa 
Published: May 2024

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/µL; HC, 1125.0 [1005.0–1236.2] pmol/µL;p< 0.05), especially sialylatedN-glycans (CIDP, 898.0 [752.2–1037.2] pmol/µL; HC, 1064.4 [942.7–1189.8] pmol/µL;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).

Conclusions

Low levels of sialylatedN-glycans may serve as a novel biomarker reflecting pathophysiology and therapeutic resistance in typical CIDP.

KEY MESSAGE

What is already known on this topic

Abnormal conformational changes in glycans of serum proteins are associated with the pathogenesis of inflammatory diseases. In a demyelinating mouse model,N-glycans suppress the activity of inflammatory helper T- and B-cells. A decrease in sialylatedN-glycans of serum IgG-Fc in the serum of patients with CIDP correlates with disease severity, suggesting the potential of serum glycans as biomarkers for CIDP.

What this study adds

In the patients with typical CIDP, serum totalN-glycans, especially sialylated types, were significantly decreased, indicating a reduction in sialylatedN-glycans derived from glycoproteins in CIDP. Moreover, lower levels of totalN-glycans, particularly α2,6-sialylatedN-glycans, were associated with reduced responsiveness to initial IVIg treatment.

How this study might affect research, practice or policy

The study’s findings provide a new approach to exploring the immunological and therapeutic aspects of the role of glycans in CIDP. The decrease in serum totalN-glycans, specifically sialylated types, may reflect an inflammatory pathophysiology in CIDP. Furthermore, it is suggested that these changes may serve as novel biomarkers to predict response to initial IVIg treatment.