Glycoproteomics of IgA1: uncovering key N-glycan composition in ankylosing spondylitis

Abstract Objective This study aimed to identify distinct IgA1 N-glycan composition in patients with ankylosing spondylitis (AS) compared with healthy controls and to explore their associations with inflammatory markers and disease activity indices. Methods Serum samples were collected from 36 patients with AS and 35 healthy controls. The diagnosis of AS was based on the New York criteria. Clinical assessments included inflammatory markers (ESR, CRP, and IgA) and disease activity indices (BASDAI, ASDAS-ESR, and ASDAS-CRP). IgA1 was isolated using affinity purification and gel filtration chromatography, followed by mass spectrometry to identify N-glycans. Results Among the 23 detected N-glycan patterns, significant differences were observed in 13 of the 18 N-glycans at the N144 site and in all five N-glycans at the N340 site between patients with AS and controls. Notably, the glycans HexNAc3Hex4NeuAc1, HexNAc4Hex4NeuAc1 and HexNAc5Hex5NeuAc1 at N144 demonstrated strong associations with all three inflammatory markers, including ESR, CRP, and IgA (P < 0.001). Levels of HexNAc4Hex4NeuAc1 were significantly elevated in patients with AS compared with those in the healthy controls. Increased sialylation and galactosylation, along with decreased fucosylation, were noted at N144 of IgA1 in patients with AS. Conversely, no glycans at N340 showed a correlation with all inflammatory markers simultaneously or with any disease activity indicators. Conclusion IgA1 from patients with AS exhibited distinct glycosylation traits compared with controls, with elevated levels of HexNAc₄Hex₄NeuAc₁ at N144 associated with inflammatory markers. These findings suggested that differential glycosylation patterns of IgA1 may play a role in the pathogenesis of AS.