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Peer-reviewedCC BY-NC 4.0Therapeutic Advances in Musculoskeletal Disease

Serum IgG N-glycosylation profiles distinguish primary Sjögren’s disease, rheumatoid arthritis, and systemic lupus erythematosus and are associated with disease activity in Sjögren’s disease

  • Zhixian Chen1,2
  • Xiaojia Xu1,2
  • Manshu Song2
  • Fengcai Shen1
  • Haifeng Hou3
  • Wei Wang2,4,5
  • Ling Lin1,6
6 affiliations
  1. 1Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
  2. 2Nutrition & Health Innovation Research Institute, School of Medical & Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
  3. 3Department of Epidemiology, School of Public Health, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China
  4. 4Institute of Glycome Study, Shantou University Medical College, Shantou, Guangdong, China
  5. 5Guangdong Laboratory of Chemistry and Fine Chemical Engineering, Shantou, Guangdong, China
  6. 6Department of Rheumatology, Shantou University Medical College, Shantou, Guangdong, China
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Abstract

Background: IgG N-glycosylation regulates immune effector functions and inflammation, but disease-specific patterns in primary Sjögren’s disease (SjD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are insufficiently defined, particularly in SjD.

Objectives: To identify serum IgG N-glycan biomarkers that differentiate SjD, RA, and SLE and reflect disease activity in SjD.

Design: A clinical case-control study.

Methods: Serum IgG N-glycans from 88 SjD patients, 102 RA patients, 86 SLE patients and 91 healthy controls were profiled using ultra-performance liquid chromatography. Discriminative glycans were selected through machine learning-based feature selection and evaluated for their diagnostic performance using cross-validated logistic regression and receiver operating characteristic (ROC) analysis.

Results: All three diseases exhibited decreased galactosylation and increased bisecting N-acetylglucosamine (GlcNAc). SjD showed the lowest sialylation (19.92%) and the highest bisecting GlcNAc levels (19.36%). Shared features included elevated GP1 (FA1) and reduced GP9 (FA2[3]G1). Compared with RA, SjD was characterized by elevated GP3 (A2B, adjusted odds ratio [AOR] 4.27), GP8 (FA2[6]G1, AOR 3.53) and reduced GP23 (FA2G2S2, AOR 0.07). Elevated GP11 (FA2[3]BG1, AOR 11.99) distinguished SjD from SLE. These glycans outperformed conventional autoantibodies in ROC analysis. In SjD, higher disease activity was associated with reduced galactosylation, with GP5 (M5) positively (AOR 1.71) and GP14 (FA2G2) inversely (AOR 0.43) associated with activity. These glycans showed stronger correlations with disease activity than erythrocyte sedimentation rate or serum IgG levels (GP5: r = 0.462; GP14: r = −0.432), and the combined glycan model achieved an AUC of 0.758.

Conclusions: Distinct IgG N-glycan signatures differentiate SjD, RA, and SLE despite their shared clinical and immunologic characteristics and are associated with disease activity in SjD. These findings provide insights into IgG N-glycosylation in these autoimmune diseases and may inform future research into their potential utility as non-invasive biomarkers, particularly in SjD.

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Cite

BibTeXRIS
BibTeX
@article{chen2026serum,
  title = {{Serum IgG N-glycosylation profiles distinguish primary Sjögren’s disease, rheumatoid arthritis, and systemic lupus erythematosus and are associated with disease activity in Sjögren’s disease}},
  author = {Zhixian Chen and Xiaojia Xu and Manshu Song and Fengcai Shen and Haifeng Hou and Wei Wang and Ling Lin},
  journal = {Therapeutic Advances in Musculoskeletal Disease},
  year = {2026},
  month = sep,
  doi = {10.1177/1759720x261488940},
  url = {https://doi.org/10.1177/1759720x261488940},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Serum IgG N-glycosylation profiles distinguish primary Sjögren’s disease, rheumatoid arthritis, and systemic lupus erythematosus and are associated with disease activity in Sjögren’s disease
AU  - Zhixian Chen
AU  - Xiaojia Xu
AU  - Manshu Song
AU  - Fengcai Shen
AU  - Haifeng Hou
AU  - Wei Wang
AU  - Ling Lin
PY  - 2026
DA  - 2026/09/17
JO  - Therapeutic Advances in Musculoskeletal Disease
DO  - 10.1177/1759720x261488940
UR  - https://doi.org/10.1177/1759720x261488940
AB  - Background: IgG N-glycosylation regulates immune effector functions and inflammation, but disease-specific patterns in primary Sjögren’s disease (SjD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are insufficiently defined, particularly in SjD.  Objectives: To identify serum IgG N-glycan biomarkers that differentiate SjD, RA, and SLE and reflect disease activity in SjD.  Design: A clinical case-control study.  Methods: Serum IgG N-glycans from 88 SjD patients, 102 RA patients, 86 SLE patients and 91 healthy controls were profiled using ultra-performance liquid chromatography. Discriminative glycans were selected through machine learning-based feature selection and evaluated for their diagnostic performance using cross-validated logistic regression and receiver operating characteristic (ROC) analysis.  Results: All three diseases exhibited decreased galactosylation and increased bisecting N-acetylglucosamine (GlcNAc). SjD showed the lowest sialylation (19.92%) and the highest bisecting GlcNAc levels (19.36%). Shared features included elevated GP1 (FA1) and reduced GP9 (FA2[3]G1). Compared with RA, SjD was characterized by elevated GP3 (A2B, adjusted odds ratio [AOR] 4.27), GP8 (FA2[6]G1, AOR 3.53) and reduced GP23 (FA2G2S2, AOR 0.07). Elevated GP11 (FA2[3]BG1, AOR 11.99) distinguished SjD from SLE. These glycans outperformed conventional autoantibodies in ROC analysis. In SjD, higher disease activity was associated with reduced galactosylation, with GP5 (M5) positively (AOR 1.71) and GP14 (FA2G2) inversely (AOR 0.43) associated with activity. These glycans showed stronger correlations with disease activity than erythrocyte sedimentation rate or serum IgG levels (GP5: r = 0.462; GP14: r = −0.432), and the combined glycan model achieved an AUC of 0.758.  Conclusions: Distinct IgG N-glycan signatures differentiate SjD, RA, and SLE despite their shared clinical and immunologic characteristics and are associated with disease activity in SjD. These findings provide insights into IgG N-glycosylation in these autoimmune diseases and may inform future research into their potential utility as non-invasive biomarkers, particularly in SjD.
SN  - 1759-720X
SN  - 1759-7218
ER  -