Plasma N-Glycome Signature of Down Syndrome.
In recent years, plasma N-glycans have emerged as biomarkers for health and disease. Here, we studied N-glycomic changes in Down Syndrome (DS). Because of the progeroid phenotype of DS, we focused on the dissection of syndrome- and aging-associated glycomic changes, as well as the interaction thereof. We analyzed the plasma N-glycome of 76 DS persons, 37 siblings (DSS), and 42 mothers (DSM) of DS persons by DNA-sequencer-aided, fluorophore-assisted-carbohydrate-electrophoresis, as well as by matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). The results showed an overall decrease of galactosylation and α2,3 sialylation, a concomitant increase of the level of fucosylated N-glycans as well as of monogalactosylated diantennary N-glycans in DS, while the GlycoAgeTest and the ratio of the two core-fucosylated, monogalactosylated diantennary isomers (galactose positioned on α1,6 arm versus α1,3 arm) were the strongest DS discriminators. Hypogalactosylation is a characteristic of both DS and aging of control individuals. A decrease in α2,3-sialylated species is also common to DS and aging of controls. However, regarding to α2,6-sialylated tri- and tetragalactosylated N-glycan species, we found those to be lowered in DS but showed an increase with age in the same persons, while these glycans were not affected by aging in control individuals. In conclusion, we identified specific glycomic changes associated with DS, aging in DS, as well as aging in controls, identifying glycomic features in line with accelerated aging in DS. Notably, our data demonstrate an aging phenotype in DS which only in part overlaps with aging in controls but reveals DS-specificity.
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna , Bologna 40138, Italy.
Vincenzo
V
Borelli
Inflammation Research Center, VIB , 9052 Ghent, Belgium.|Department of Biomedical Molecular Biology, UGent , 9052 Ghent, Belgium.
Valerie
V
Vanhooren
Center for Proteomics and Metabolomics, Leiden University Medical Center , 2333 ZA Leiden, The Netherlands.
Emanuela
E
Lonardi
Center for Proteomics and Metabolomics, Leiden University Medical Center , 2333 ZA Leiden, The Netherlands.
Karli R
KR
Reiding
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna , Bologna 40138, Italy.
Miriam
M
Capri
Inflammation Research Center, VIB , 9052 Ghent, Belgium.|Department of Biomedical Molecular Biology, UGent , 9052 Ghent, Belgium.
Claude
C
Libert
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna , Bologna 40138, Italy.|Interdepartmental Centre "L. Galvani" for Integrated Studies of Bioinformatics, Biophysics and Biocomplexity (CIG), University of Bologna , 40126 Bologna, Italy.
Paolo
P
Garagnani
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna , Bologna 40138, Italy.
Stefano
S
Salvioli
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna , Bologna 40138, Italy.|Interdepartmental Centre "L. Galvani" for Integrated Studies of Bioinformatics, Biophysics and Biocomplexity (CIG), University of Bologna , 40126 Bologna, Italy.|IRCCS, Institute of Neurological Sciences of Bologna , 40139 Bologna, Italy.|IGM-CNR Institute of Molecular Genetics, Unit of Bologna IOR , 40136 Bologna, Italy.
Claudio
C
Franceschi
Center for Proteomics and Metabolomics, Leiden University Medical Center , 2333 ZA Leiden, The Netherlands.|Division of BioAnalytical Chemistry, VU University Amsterdam , 1081 HV Amsterdam, The Netherlands.|Department of Molecular Cell Biology and Immunology, VU University Medical Center , 1007 MB Amsterdam, The Netherlands.
Manfred
M
Wuhrer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002648:Child; D004314:Down Syndrome / Q000097:blood* / Q000473:pathology; D005260:Female; D005643:Fucose / Q000097:blood / Q000737:chemistry; D005690:Galactose / Q000097:blood / Q000737:chemistry; D054794:Glycomics / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009035:Mothers; D011134:Polysaccharides / Q000097:blood* / Q000737:chemistry; D012794:Sialic Acids / Q000097:blood / Q000737:chemistry; D035781:Siblings; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011134:Polysaccharides; D012794:Sialic Acids; D005643:Fucose; D005690:Galactose
DSA-FACE; Down Syndrome; GlycoAgeTest; MALDI-TOF-MS; N-glycome; aging; ethyl esterification