Background Alterations in immunoglobulin G (IgG) N-glycosylation have been implicated in various diseases, potentially including ankylosing spondylitis (AS). However, empirical evidence regarding the associations IgG N-glycosylation, inflammatory factors, and AS is sparse. We aimed to investigate these associations and evaluate the diagnostic performance of IgG glycosylation traits as a biomarker for AS. Methods This case–control study recruited 142 AS patients and 142 controls. We used hydrophilic interaction liquid chromatography with ultra-performance liquid chromatography to detect the profiles of plasma IgG N-glycans. An enzyme-linked immunosorbent assay kit was used to measure the levels of serum inflammatory factors. We used multivariate logistic regression, canonical correlation analysis (CCA), and Lasso regression to analyze the data. Results Multivariate logistic analysis identified 14 IgG N-glycan-derived traits significantly associated with AS. The changes were primarily characterized by decreased galactosylation, sialylation, bisgalactosylated fucosylation and sialated fucosylation, alongside increased core fucosylation, agalactosylated fucosylation, neutral fucosylation and sialated bisecting N-acetylglucosamine. Significant differences were observed between cases and controls in levels of C-reactive protein (CRP), IL-17, IL-22, IL-6, and TNF-α. CCA demonstrated a moderate correlation between IgG N-glycan-derived traits and inflammatory factors (r = 0.476). The combined diagnostic performance of derived traits and inflammatory factors yielded a higher area under the curve (AUC = 0.90) than either alone (AUCderived traits = 0.88, AUCinflammatory factors = 0.78). Conclusion The findings indicate that abnormal IgG N-glycosylation may play an important role in the development of AS through promoting the pro-inflammatory function. The derived traits combined with inflammatory factors may serve as potential biomarkers to distinguish AS. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • We comprehensively analyzed IgG N-glycan-derived traits in AS by an HILIC-UPLC-based high-throughput method. • Abnormal IgG N-glycosylation plays a role in the development of AS through promoting the proinflammatory. • IgG N-glycosylation combined with inflammatory factors demonstrated strong diagnostic performance for AS. </entry> </row> </tbody> </tgroup> </Table>

Association between immunoglobulin G N-glycosylation, inflammatory factors, and ankylosing spondylitis: A case–control study

期刊论文
发表日期：

2025年9月15日

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Jia Yin,
Xuan Yin,
Lei Tao,
Yuanzhi Peng,
Shuhan Zhao,
Haifeng Hou,
Xinyue Yin,
Zhangshen Ran,
Aihong Zhou,
Guoyong Ding

摘要

Background

Alterations in immunoglobulin G (IgG) N-glycosylation have been implicated in various diseases, potentially including ankylosing spondylitis (AS). However, empirical evidence regarding the associations IgG N-glycosylation, inflammatory factors, and AS is sparse. We aimed to investigate these associations and evaluate the diagnostic performance of IgG glycosylation traits as a biomarker for AS.

Methods

This case–control study recruited 142 AS patients and 142 controls. We used hydrophilic interaction liquid chromatography with ultra-performance liquid chromatography to detect the profiles of plasma IgG N-glycans. An enzyme-linked immunosorbent assay kit was used to measure the levels of serum inflammatory factors. We used multivariate logistic regression, canonical correlation analysis (CCA), and Lasso regression to analyze the data.

Results

Multivariate logistic analysis identified 14 IgG N-glycan-derived traits significantly associated with AS. The changes were primarily characterized by decreased galactosylation, sialylation, bisgalactosylated fucosylation and sialated fucosylation, alongside increased core fucosylation, agalactosylated fucosylation, neutral fucosylation and sialated bisecting N-acetylglucosamine. Significant differences were observed between cases and controls in levels of C-reactive protein (CRP), IL-17, IL-22, IL-6, and TNF-α. CCA demonstrated a moderate correlation between IgG N-glycan-derived traits and inflammatory factors (r = 0.476). The combined diagnostic performance of derived traits and inflammatory factors yielded a higher area under the curve (AUC = 0.90) than either alone (AUC_{derived traits} = 0.88, AUC_{inflammatory factors} = 0.78).

Conclusion

The findings indicate that abnormal IgG N-glycosylation may play an important role in the development of AS through promoting the pro-inflammatory function. The derived traits combined with inflammatory factors may serve as potential biomarkers to distinguish AS.

Key Points

• We comprehensively analyzed IgG N-glycan-derived traits in AS by an HILIC-UPLC-based high-throughput method.

• Abnormal IgG N-glycosylation plays a role in the development of AS through promoting the proinflammatory.

• IgG N-glycosylation combined with inflammatory factors demonstrated strong diagnostic performance for AS.