engleski

Immunoglobulin G glycosylation in people with Down syndrome

Down syndrome (DS) is a condition caused by full or partial trisomy of chromosome 21. One of the characteristics of DS are premature signs of aging. Premature aging has many notable consequences for the entire organism, especially for the central nervous system and for the immune system. Its signs are also visible on the cellular level, as cells of people with DS show signs of DNA damage accumulation and increased levels of aging markers on an epigenetic level. However, the mechanisms causing premature aging in DS are still unknown, but some possible explanations range from amplified chromosomal instability, to increased actions of specific genes from chromosome 21. Immunoglobulin G (IgG) is an important effector molecule of the immune system that contains a highly conserved N-glycosylation site. The composition of glycans bound to IgG is crucial for its structure and function. Changes in IgG glycosylation are an accurate predictor of chronological and biological age and have also been correlated to various diseases. Comparison of IgG glycosylation of n=208 adults with DS from three different European populations (n=98 from France, n=57 from Italy, n=53 from the UK) to age-, sex-, and demography-matched healthy populations showed results consistent with the presence of premature aging in DS. More specifically, glycan traits known to change with age (glycans without galactose, G0 ; and glycans with two galactoses, G2) were observed to be significantly shifted in persons with DS in the direction typically associated with aging, namely the levels of G0 increased and G2 decreased. G0 and G2 values of DS individuals were characteristic for on average 19 years older heathy individuals. In addition, glycans with core fucose (F) were increased whereas glycans with sialic acid (S) were decreased in persons with DS compared to healthy individuals. Comparison of IgG glycosylation was also done between sub-groups of people with DS with and without certain comorbidities (namely dementia, autoimmune disease, thyroid disease, and frequent respiratory infections) and healthy populations to correct for the effect of DS-related comorbidities on IgG glycosylation. The results of this comparison were consistent with the previous comparison of DS as a whole group undivided by comorbidities, suggesting these changes are truly the effect of DS and not of the comorbidities. The same changes (increased G0 and nominally decreased G2) were also observed in children with DS when compared to healthy children, suggesting that these changes start very early in life. This is the first research to analyse IgG glycosylation in DS and show non- epigenetic evidence of systematic premature aging in DS.

immunoglobulin G, glycosylation, Down syndrome

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