Dataset Information

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.

SUBMITTER: Barrios C

PROVIDER: S-EPMC4769202 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Glycosylation Profile of IgG in Moderate Kidney Dysfunction.

Barrios Clara C Zierer Jonas J Gudelj Ivan I Štambuk Jerko J Ugrina Ivo I Rodríguez Eva E Soler María José MJ Pavić Tamara T Šimurina Mirna M Keser Toma T Pučić-Baković Maja M Mangino Massimo M Pascual Julio J Spector Tim D TD Lauc Gordan G Menni Cristina C

Journal of the American Society of Nephrology : JASN 20150716 3

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 populat ...[more]

PMID: 26185202

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Project description:Exercise is known to improve many aspects of human health, including modulation of the immune system and inflammatory status. It is generally understood that exercise reduces inflammation, but there are missing links in terms of understanding the mechanisms as well as the differences between exercise modalities. N-glycosylation of immunoglobulin G (IgG) and total plasma proteins was previously shown to reflect changes in inflammatory pathways, which could provide valuable information to further clarify exercise effects. In order to further expand the understanding of the relationship between physical activity and inflammation, we examined the effect of intense exercise, in the form of repeated sprint training (RST), on IgG and total plasma proteins N-glycosylation in combination with traditionally used inflammation markers: C-reactive protein (CRP), interleukin 6 (IL-6), and leukocyte count. Twenty-nine male physical education students were separated into treatment (RST, N = 15) and control (N = 14) groups. The RST group completed a 6-week exercise protocol while the control group was instructed to refrain from organized physical activity for the duration of the study. Three blood samples were taken at different time points: prior to start of the training program, the final week of the exercise intervention (EXC), and at the end of the 4-week recovery period (REC). Following the end of the recovery period IgG N-glycosylation profiles showed anti-inflammatory changes in RST group compared to the control group, which manifested as a decrease in agalactosylated (p = 0.0473) and an increase in digalactosylated (p = 0.0473), and monosialylated (p = 0.0339) N-glycans. Plasma protein N-glycans didn't change significantly, while traditional inflammatory markers also didn't show significant change in inflammatory status. Observed results demonstrate the potential of intense physical exercise to reduce levels of systemic basal inflammation as well as the potential for IgG N-glycosylation to serve as a sensitive longitudinal systemic inflammation marker.

Project description:BackgroundEnd-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.MethodsObservational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.ResultsThere were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.ConclusionsIn people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Dataset Information

Glycosylation Profile of IgG in Moderate Kidney Dysfunction.

Publications

Glycosylation Profile of IgG in Moderate Kidney Dysfunction.

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