Dataset Information

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

ABSTRACT:

Background

Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension.

Methods

The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n?=?78) and cerebral arterial stenosis (CAS) (n?=?75) and controls (n?=?77) were analyzed by ultra-performance liquid chromatography.

Results

Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver-operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732-0.872) and controls (AUC, 0.740; 95% CI, 0.661-0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r?=?0.566, p?ConclusionOur findings indicated that loss of galactose and sialic acid, as well as addition of bisecting GlcNAc, might involve in pro- or anti-inflammatory IgG functionality and further contribute to the pathogenesis of IS. IgG glycan profiles may be developed as clinical useful biomarkers for chronic disease in the future.

SUBMITTER: Liu D

PROVIDER: S-EPMC5921323 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

Liu Di D Zhao Zhongyao Z Wang Anxin A Ge Siqi S Wang Hao H Zhang Xiaoyu X Sun Qi Q Cao Weijie W Sun Ming M Wu Lijuan L Song Manshu M Zhou Yong Y Wang Wei W Wang Youxin Y

Journal of neuroinflammation 20180426 1

<h4>Background</h4>Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension.<h4>Methods</h4>The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition ...[more]

PMID: 29699572

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Project description:Rationale: Stroke is a leading causes of human death worldwide. Ischemic damage induces the sterile neuroinflammation, which directly determines the recovery of patients. Lipids, a major component of the brain, significantly altered after stroke. Cholesterol sulfate, a naturally occurring analog of cholesterol, can directly regulate immune cell activation, indicating the possible involvement of cholesterol metabolites in neuroinflammation. Sulfotransferase family 2b member 1 (Sult2b1) is the key enzyme that catalyzes the synthesis of cholesterol sulfate. This study aimed to investigate the function of Sult2b1 and cholesterol sulfate in the neuroinflammation after ischemic stroke. Methods and Results: Sult2b1 -/- and wild-type mice were subjected to transient middle cerebral artery occlusion. Our data showed that Sult2b1 -/- mice had larger infarction and worse neurological scores. To determine whether immune cells were involved in the worsening stroke outcome in Sult2b1 -/- mice, bone marrow transplantation, immune cell depletion, and adoptive monocyte transfer were performed. Combined with CyTOF and immunofluorescence techniques, we demonstrated that after stroke, the peripheral monocyte-derived macrophages were the dominant cell type promoting the pro-inflammatory status in Sult2b1 -/-mice. Using primary bone marrow-derived macrophages, we showed that cholesterol sulfate could attenuate the pro-inflammatory polarization of macrophages under both normal and oxygen-glucose deprivation conditions by regulating the levels of nicotinamide adenine dinucleotide phosphate (NADPH), reactive oxygen species (ROS), and activating the AMP-activated protein kinase (AMPK) - cAMP responsive element-binding protein (CREB) signaling pathway. Conclusions: Sult2b1 -/- promoted the polarization of macrophages into pro-inflammatory status. This trend could be attenuated by adding cholesterol sulfate, which promotes the polarization of macrophages into anti-inflammatory status by metabolic regulation. In this study, we established an inflammation-metabolism axis during the macrophage polarization after ischemic stroke.

Project description:Ischemic heart disease (IHD) is clinical manifestation of chronic inflammatory progressive pathological process of atherosclerosis in coronary arteries. IHD is the leading cause of morbidity and mortality in the world. The question is whether it is possible to improve and direct the therapeutic treatment of IHD patients in the treatment of the inflammatory process in the atherosclerotic leasions.A prospective, comparative, analytica,clinically applicable, open-type study was performed. The study was conducted on 80 subjects with controlled biohumoral markers: troponin, CK, CK MB, BNP; markers of atherogenesis: LDL and homocystein; inflammatory markers: CRP, amyloid, cytokines IL-2, IL-6,TNF-alpha. The experimental group of 38 respondents had in addition to the conventional IHD treatment with: ampicillin (which included organosulfur compounds), cyancobalamin, vitamin B complex (B1, B2 and B6) and folacin. A control group of 42 respondents did not have this additional treatment.Major adverse cardic events (MACE) such as postinfarctic angina pectoris and repeated infarction, need for surgical interventions of myocardial revascularization, signs of cardiac insufficiency and death were observed during the one-year period. There was no correlation between the IL-2, IL-6 and TNF-alpha, as well as CK, CKMB and troponin and MACE in one-year follow-up. There was a strong positive correlation between MACE and CRP (p = 0,0002) and amyloid (p = 0,0005) as inflamatory markers; a strong positive correlation between MACE and homocysteine as an atherogenic marker (p = 0,0002, and amoderate positive correlation between MACE and BNP (p = 0.0403) as ischemic marker and marker of cardiac insufficiency. The echocardiographically monitored systolic function showed a moderate difference in the groups with average higher values in the experimantal group (p = 0.0282).The applied treatment exhibited a moderate positive effect on the systolic function of LV and significantly reduced the MACE in the work compared to the control group (p <0.0001), and demonstrated a potential anti-inflammatory effect.

Dataset Information

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

Background

Methods

Results

Publications

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

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