Xu Xiaojia, Chen Zhixian, Song Manshu, Hou Zhiduo, Balmer Lois, Zhou Chunbin, Huang Yayi, Hou Haifeng, Wang Wei, Lin Ling
Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China.
Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, 6027, Australia.
Arthritis Res Ther. 2025 Feb 22;27(1):37. doi: 10.1186/s13075-025-03505-y.
Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease with challenges in diagnosis and disease activity assessment. While alterations in immunoglobulin G (IgG) N-glycosylation have been observed in varied rheumatic diseases, those in axSpA remains unclear. This study aims to explore the role of IgG N-glycan profiles in diagnosis and disease activity of axSpA.
A clinical case-control study was conducted involving patients with axSpA (n = 138), systemic lupus erythematosus (n = 102), rheumatoid arthritis (n = 106), osteoarthritis (n = 33), gout (n = 41) and healthy controls (n = 117). Ultra-performance liquid chromatography was employed to analyze the composition of the serum IgG N-glycome. Associations between IgG N-glycans and axSpA were investigated and compared to healthy controls and other four rheumatic diseases. The relationship among IgG N-glycosylation, disease activity, and inflammatory cytokines of axSpA patients were analyzed. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic/classification performance of IgG N-glycans to distinguish axSpA and its disease activity.
In patients with axSpA, the abundances of IgG galactosylation and sialylation were significantly lower than healthy controls, while the abundance of fucosylation was higher than the other four studied rheumatic diseases. Additionally, two asialylated IgG N-glycans (FA2 and FA2 [3]G1) were associated with axSpA, with adjusted odds ratios (AORs) of 5.62 (95% CI: 3.41-9.24) and 0.33 (95% CI: 0.22-0.50), respectively. Notably, decreased FA2 [3]G1 emerged as a characteristic IgG N-glycan associated with all five studied rheumatic diseases, while decreased FA2BG2S2 was a unique IgG N-glycan differentiating axSpA from the other four rheumatic diseases. Furthermore, FA2 displayed positive association with disease activity indicators (ASDAS-CRP, SPARCC-SIJ and SPARCC-spine) in axSpA. IgG N-glycans, particularly FA2 [3]G1, FA2BG2S2 and FA2, demonstrated canonical correlation with inflammatory cytokines, including interleukin-23 and tumor necrosis factor α, in axSpA (r = 0.519, P = 0.017).
Specific IgG N-glycans hold potential as novel biomarkers to enhance diagnosis and disease activity assessment in axSpA management.
轴性脊柱关节炎（axSpA）是一种炎症性风湿性疾病，在诊断和疾病活动评估方面存在挑战。虽然在多种风湿性疾病中已观察到免疫球蛋白G（IgG）N-糖基化的改变，但axSpA中的情况仍不清楚。本研究旨在探讨IgG N-聚糖谱在axSpA诊断和疾病活动中的作用。
进行了一项临床病例对照研究，纳入axSpA患者（n = 138）、系统性红斑狼疮患者（n = 102）、类风湿关节炎患者（n = 106）、骨关节炎患者（n = 33）、痛风患者（n = 41）和健康对照者（n = 117）。采用超高效液相色谱法分析血清IgG N-糖组的组成。研究IgG N-聚糖与axSpA之间的关联，并与健康对照者和其他四种风湿性疾病进行比较。分析axSpA患者IgG N-糖基化、疾病活动和炎性细胞因子之间的关系。应用受试者工作特征（ROC）曲线分析评估IgG N-聚糖区分axSpA及其疾病活动的诊断/分类性能。
在axSpA患者中，IgG半乳糖基化和唾液酸化的丰度显著低于健康对照者，而岩藻糖基化的丰度高于其他四种研究的风湿性疾病。此外，两种去唾液酸化的IgG N-聚糖（FA2和FA2 [3]G1）与axSpA相关，调整后的优势比（AOR）分别为5.62（95%CI：3.41 - 9.24）和0.33（95%CI：0.22 - 0.50）。值得注意的是，FA2 [3]G1的减少是与所有五种研究的风湿性疾病相关的特征性IgG N-聚糖，而FA2BG2S2的减少是区分axSpA与其他四种风湿性疾病的独特IgG N-聚糖。此外，FA2与axSpA的疾病活动指标（ASDAS-CRP、SPARCC-SIJ和SPARCC-脊柱）呈正相关。在axSpA中，IgG N-聚糖，特别是FA2 [3]G1、FA2BG2S2和FA2，与炎性细胞因子（包括白细胞介素-23和肿瘤坏死因子α）呈典型相关性（r = 0.519，P = 0.017）。
特定的IgG N-聚糖有潜力作为新型生物标志物，以加强axSpA管理中的诊断和疾病活动评估。
