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Immunoglobulin G glycosylation in people with Down syndrome in three different European populations

Down syndrome (DS) is a condition caused by trisomy of chromosome 21. Persons with DS show signs of premature aging which are visible on the level of the entire organism and on the cellular level. Cells of people with DS accumulate DNA damage and show increased levels of epigenetic aging markers [1]. The mechanisms causing premature aging in DS are yet to be determined, but it has been suggested that premature aging in DS could result from amplified chromosomal instability or increased actions of specific genes from chromosome 21. Immunoglobulin G (IgG) contains a highly conserved N-glycosylation site, IgG glycans have been shown to be accurate predictors of chronological and biological age and have also been correlated to various diseases [2]. Comparison of IgG glycosylation of 208 adults with DS from three different European populations to age-, sex-, and demography-matched healthy controls showed results consistent with the presence of premature aging in DS. Glycan traits known to change with age (glycans without galactose, G0 ; and glycans with two galactoses, G2) were significantly shifted in persons with DS in the direction typically associated with aging – the levels of G0 increased and G2 decreased. Also, glycans with core fucose (F) were increased and glycans with sialic acid (S) were decreased in persons with DS. Comparison of IgG glycosylation was also done between healthy controls and sub- groups of people with DS with and without certain comorbidities to correct for the effect of comorbidities on IgG glycosylation. The obtained results showed that most of the IgG glycosylation changes observed in persons with DS were the effect of DS and not of the comorbidities. The same changes in G0 and G2 were also observed in children with DS, suggesting that these changes start 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. [1] Murray A et al. Brief report: isogenic induced pluripotent stem cell lines from an adult with mosaic down syndrome model accelerated neuronal ageing and neurodegeneration. Stem Cells. 2015 Jun ; 33(6):2077-84. [2] Gudelj I, Lauc G, Pezer M. Immunoglobulin G glycosylation in aging and diseases. Cell Immunol. 2018 Nov ; 333:65-79.

immunoglobulin G, glycosylation, Down syndrome

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