title: Glycosylation Profile of IgG in Moderate Kidney Dysfunction.
abstract: Glycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P<6.5×10(-4)) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom; Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain; cristina.menni@kcl.ac.uk CBarrios@parcdesalutmar.cat.
authors.forename: Clara
authors.initials: C
authors.lastname: Barrios
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Munich, Germany;
authors.forename: Jonas
authors.initials: J
authors.lastname: Zierer
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gudelj
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia; and.
authors.forename: Jerko
authors.initials: J
authors.lastname: Štambuk
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia; and.
authors.forename: Ivo
authors.initials: I
authors.lastname: Ugrina
authors.affiliation: Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain;
authors.forename: Eva
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain;
authors.forename: María José
authors.initials: MJ
authors.lastname: Soler
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Pavić
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Mirna
authors.initials: M
authors.lastname: Šimurina
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Toma
authors.initials: T
authors.lastname: Keser
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia; and.
authors.forename: Maja
authors.initials: M
authors.lastname: Pučić-Baković
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom;
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain;
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom;
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia; and University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom; cristina.menni@kcl.ac.uk CBarrios@parcdesalutmar.cat.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005690:Galactose / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D011134:Polysaccharides / Q000097:blood* / Q000737:chemistry; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D011134:Polysaccharides; C064155:agalactosyl IGG; D000117:Acetylglucosamine; D005690:Galactose
keywords: clinical nephrology; glycation; renal function decline