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N-glycosylation of IgG is not influenced by the level of renal complications or retinopathy in type 1 diabetes mellitus

N-glycosylation of immunoglobulin G (IgG) is known to influence the antibody function. Changes in IgG N- glycome associate with many inflammatory conditions and were reported in early stages of type 1 and type 2 diabetes mellitus (DM). IgG N- glycosylation was also studied in relation to disease progression in type 2 DM and was found to associate with diabetes complications. Although type 1 and type 2 DM share complications, these findings may not apply to type 1 DM due to different pathophysiology involved and a longer disease duration prior to complication manifestation. In this study we investigated IgG N- glycosylation of 190 patients (age 18-70, median 46, 81 M, 109 F) with type 1 complications. Complications included: hypertension, albuminuria and retinopathy. Patients were differentiated by the levels of complications but were all in later stages of disease progression. N-linked glycans from IgG were released, fluorescently labelled and analysed using HILIC-UPLC. Twenty-four glycan structures were identified and relatively quantified. In addition, nine derived traits, corresponding to different structural characteristics of glycans were calculated. Data was analysed using multiple linear regression with age and sex as covariates. Glycan traits were log transformed prior to analysis. We observed no statistically significant changes of IgG N- glycosylation with respect to type of complication or severity level. Previously reported changes with respect to age, sex and lifestyle aspects, e.g., smoking were replicated in this study, confirming their influence on the glycome. IgG N- glycosylation changes previously reported as connected to the severity of complications in type 2 DM were not replicated for type 1 DM patients in our study. This can be explained by the fact that pathophysiological changes leading to type 1 DM and influencing the N- glycome occur much earlier in life and are not further influenced by disease progression and development of complications in the adult age. Absence of differences with respect to type of complications may also be due to fact that they share some common pathophysiological processes which prevent their distinction based on IgG N- glycosylation profile.

glycosylation, N-glycosylation, IgG, diabetes, type 1 diabetes

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