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. 2025 Jun 18:16:1538219.
doi: 10.3389/fimmu.2025.1538219. eCollection 2025.

N-glycosylation patterns of plasma immunoglobulin G in anti-synthetase syndrome disease

Jing Zhao #  1 , Yanhong Li #  1 , Yingying Ling #  1 , Tong Wu  1 , Yinlan Wu  1 , Chunyu Tan  1 , Lu Cheng  1 , Deying Huang  1 , Yi Liu  1 , Yong Zhang  1
Affiliations

N-glycosylation patterns of plasma immunoglobulin G in anti-synthetase syndrome disease

Jing Zhao et al. Front Immunol. .

Abstract

Introduction: Anti-synthetase syndrome (ASS) is a subtype of idiopathic inflammatory myopathy (IIM) characterized by characteristic rash, myositis, and interstitial lung disease (ILD). The etiology of ASS is unknown, and patients have a poor quality of life and are prone to pulmonary infection. Recent studies have elucidated the potential role of abnormal glycosylation of immunoglobulin G (IgG) in the pathogenesis of autoimmune diseases. However, the pattern of patient-specific IgG N-glycosylation in ASS has not been fully elucidated.

Methods: the GlycoQuant method was used to quantify the intact N-glycopeptides of IgG from 30 ASS patients and 30 healthy controls (HCs).

Results and discussion: Thirteen differentially expressed intact N-glycopeptides were identified (p<0.05). Notably, we observed increased fucosylation (p<0.0001) and decreased N-acetylneuraminic acid (p<0.05) in ASS patients. In addition, specific glycosylation patterns correlated with lung function parameters. Our study revealed the IgG glycosylation profile in ASS patients and provided a valuable reference for further investigation of its potential diagnostic and prognostic applications.

Keywords: N-glycosylation; anti-synthetase syndrome (ASS); autoimmune disease; immunoglobulin g (IgG); intact N-glycopeptide.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of the workflow for the analysis of IgG intact N-glycopeptides via the GlycoQuant method.
Figure 2
Figure 2
Differences in IgG N-glycans between the ASS and HC groups. This figure highlights the significant variations in N-glycosylation patterns observed between the ASS and HC groups. (A) N3H3F1, (B)N4H3F1, (C)N3H4F1, (D) N4H4, (E) N4H4F1, (F) N4H5F1, (G) N4H5F1A1, (H) N5H4F1, (I) N5H5F1. H, hexose; N, N-acetylhexosamine; F, fucose; A, N-acetylneuraminic acid. **p<0.005, ***p<0.001, ****p<0.0001.
Figure 3
Figure 3
Characteristics of IgG N-glycans containing fucose (A) and N-acetylneuraminic acid (B) in the ASS and HC groups. *p <0.05, **** p<0.0001.
Figure 4
Figure 4
Differences in intact N-glycopeptides of IgG between the ASS and HC groups. (A) IgG1-N4H3F1, (B) IgG1-N4H4F1, (C) IgG2-N3H3F1, (D) IgG2-N4H3F1, (E) IgG3-N4H4F1, (F) IgG3-N4H3F1, (G) IgG2-N3H4F1, (H) IgG2-N4H4, (I) IgG2-N4H4F1, (J) IgG2-N4H5F1A1, (K) IgG2-N4H5F1, (L) IgG2-N5H4F1, (M) IgG2-N5H5F1. *p <0.05, **p<0.005, ***p<0.001, **** p<0.0001.
Figure 5
Figure 5
Heatmap depicting the correlation between IgG intact N-glycopeptides and the clinical manifestations of ASS. *Indicates a statistically significant correlation between the N-glycopeptide and the clinical indicators in ASS patients, with *p <0.05. BMI, bode-mass index; MITAX, myositis intention to treat activity index; ILD, interstitial lung disease; cNSIP, cell nonspecific interstitial pneumonia; OP, organizing pneumonia; Ro52, anti-cytoplasmic ribonucleoprotein of 52 kDa; ANA, antinuclear antibody; ALP, alkaline phosphatase; TP, total protein; ALB, albumin; GLB, globulin; Cre, creatinine; eGFR, estimated glomerular filtration rate; TG, triglyceride; LDL, low-density lipoprotein; Hb, hemoglobin; WBC, white blood cell count; RBC, red blood cell count; LYM, lymphocyte; MONO, monocyte; CRP, C-reactive protein; IgG, immunoglobulin G; IgA, immunoglobulin A; C3, complement C3; C4, complement C4; pro-BNP, pro-brain natriuretic peptide; FVC, forced vital capacity; VC, vital capacity; RV, residual volume; TLC, total lung capacity; DLCO, diffusing capacity of the lung for carbon monoxide.
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