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Aims
To identify N-glycan structures on immunoglobulin A related to type 1 diabetes mellitus among children at the disease onset and adults with type 1 diabetes mellitus.
Methods
Human polyclonal IgA N-glycans were profiled using hydrophilic interaction ultra performance liquid chromatography in two cohorts. The first cohort consisted of 62 children at the onset of type 1 diabetes mellitus and 86 of their healthy siblings. The second cohort contained 84 adults with the disease and 84 controls. Associations between N-glycans and type 1 diabetes mellitus were tested using linear mixed model for the paediatric cohort, or general linear model for the adult cohort. False discovery rate was controlled by Benjamini-Hochberg method modified by Li and Ji.
Results
In children, an increase in a single oligomannose N-glycan was associated with type 1 diabetes mellitus (B = 0.529, p = 0.0067). N-glycome of the adults displayed increased branching (B = 0.466, p = 0.0052), trigalactosylation (B = 0.466, p = 0.0052), trisialylation (B = 0.629, p < 0.001), and mannosylation (B = 0.604, p < 0.001). The strongest association with the disease was a decrease in immunoglobulin A core fucosylation (B = −0.900, p < 0.001).
Conclusions
Changes in immunoglobulin N-glycosylation patterns in type 1 diabetes point to disruptions in immunoglobulin A catabolism and dysregulated inflammatory capabilities of the antibody, potentially impacting immune responses and inflammation.
Sources - https://www.sciencedirect.com/science/article/pii/S2405844024065605