The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia

Abstract

BackgroundAlternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension.MethodsHerein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20–68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography.ResultsBlood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644–0.740).ConclusionsOur findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1616-2) contains supplementary material, which is available to authorized users.

Next-Generation (Glycomic) Biomarkers for Cardiometabolic Health: A Community-Based Study of Immunoglobulin G N-Glycans in a Chinese Han Population

“…Our previous studies have shown that the decreasing galactosylation and sialylation and the increasing bisecting GlcNAc are risk factors of many inflammatory and chronic diseases (Adua et al, 2017), including hypertension (Wang et al, 2016b), stroke (Liu et al, 2018b), T2DM (Lemmers et al, 2017), and dyslipidemia (Liu et al, 2018a), which are consistent with this study. The changes to IgG N-glycans, which were reported in metabolic syndrome, hypertriglyceridemic waist phenotype, and abdominal obesity in this study, might suggest that aberrant glycosylation of IgG is not disease specific, but a general phenomenon associated with reducing the anti-inflammatory function of circulating IgG.…”

“…These findings indicate that high levels of agalactosylated N-glycans and bisecting GlcNAc may be associated with higher measures of hypertriglyceridemic waist phenotype, which may increase the risk of coronary artery disease. These findings are strongly supported by previous evidence that GP5 and GP11 are positively associated with dyslipidemia (Liu et al, 2018a). Therefore, GP5, GP10, GP 11, and GP15…”

“…Previous glycomics research has shown that IgG Nglycans are associated with the cardiometabolic risk factors, including hypertension (Gao et al, 2017;Liu et al, 2018c;Wang et al, 2016b), T2DM (Ge et al, 2018;Lemmers et al, 2017), central obesity (Russell et al, 2018), and dyslipidemia (Liu et al, 2018a). In this study, we described the association of IgG N-glycans with the 15 cardiometabolic risk factors in a Chinese Han population.…”

“…In addition, total plasma N-glycans have been shown to be associated with risk factors of metabolic syndrome (Lu et al, 2011;McLachlan et al, 2016). The inflammatory role of IgG N-glycans, together with their association with the cardiometabolic risk factors, such as aging , central obesity (Russell et al, 2018), dyslipidemia (Liu et al, 2018a), and hyperglycemia (Ge et al, 2018), leads to the hypothesis of this study that the changes to IgG N-glycan profiles are involved in the pathogenesis of cardiometabolic disease by regulating the inflammatory response.…”

Genetic and functional evidence relates a missense variant inB4GALT1to lower LDL-C and fibrinogen

“…Also, reduced LDLR glycosylation was found to result in reduced lipid binding and endocytosis 41 . Recently, changes in IgG glycosylation have been associated with blood lipids and dyslipidemia in Han Chinese 42 . A similar role for glycosylation was also reported in relation to coagulation proteins, where mutations affecting glycosylation were associated with different enzymatic activity 37 .…”