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INVESTIGATING THE N-GLYCOSYLATION OF IMMUNOGLOBULIN A IN TYPE 1 DIABETES

N-glycosylation is a strictly regulated enzymatic reaction during which complex oligosaccharides are covalently attached to proteins, thus impacting their function [1]. One of such proteins is immunoglobulin A (IgA), a heavily glycosylated antibody which plays a key role in the immune system. Glycans modulate its various roles, including antigen binding and the antibody effector functions [2]. Despite its significance, N-glycosylation of IgA remains largely underexplored in autoimmune diseases, including type 1 diabetes (T1D). Former studies on IgA in T1D have focused mostly on its serum levels, suggesting a disruption of IgA catabolism [3]. In this study, we analyzed serum IgA N-glycosylation in 86 children at the onset and 63 of their healthy siblings, as well as in 90 adults with T1D and 90 healthy controls using a high-throughput UPLC approach. N-glycome was divided into 30 glycan groups from which 12 derived traits were calculated based on structural similarities. Our study identified IgA N- glycan traits characteristic of T1D and revealed differences in the N-glycosylation patterns of IgA between children at T1D onset and adults with T1D. In children, IgA N-glycoprofile remained mostly unchanged compared to their healthy siblings, with only one oligomannose N-glycan significantly increased. IgA N-glycome in adults exhibited a shift towards complex high-branched, trigalactosylated and trisialylated as well as oligomannosylated glycans, while the most prominent association with T1D was a decrease in total core fucosylation. These findings indicate a transition of IgA N-glycosylation in T1D toward patterns characteristic of total plasma proteins in various inflammatory conditions.

immunoglobulin A, N-glycosylation, type 1 diabetes

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