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J Am Soc Nephrol. 2016 Mar;27(3):933-41. doi: 10.1681/ASN.2015010109. Epub 2015 Jul 16.

Glycosylation Profile of IgG in Moderate Kidney Dysfunction.

Author information

1
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.
2
Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Munich, Germany;
3
Genos Glycoscience Research Laboratory, Zagreb, Croatia; and.
4
Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain;
5
University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
6
Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom;
7
Genos Glycoscience Research Laboratory, Zagreb, Croatia; and University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
8
Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom; cristina.menni@kcl.ac.uk CBarrios@parcdesalutmar.cat.

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.

KEYWORDS:

clinical nephrology; glycation; renal function decline

PMID:
26185202
PMCID:
PMC4769202
DOI:
10.1681/ASN.2015010109
[Indexed for MEDLINE]
Free PMC Article

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