背景:动脉粥样硬化被认为是认知功能下降的发病机理中的重要组成部分,如发生在血管性认知障碍(VCI)。炎症和免疫反应在许多慢性疾病的发展中起着重要作用。免疫球蛋白G(IgG)N-糖基化通过影响IgG的抗炎和促炎反应而参与多种疾病的发展。本研究旨在通过病例对照研究,探讨动脉粥样硬化患者样本中IgGN-糖基化与VCI之间的关系。
方法:我们共招募了330例动脉粥样硬化患者参与本病例对照研究,包括165名VCI患者和165名性别和年龄匹配的认知功能正常的参与者。通过超高效液相色谱法分离参与者的血浆IgGN-聚糖。采用酶联免疫吸附试验(ELISA)试剂盒测定相应的血清炎症因子。颈动脉超声诊断动脉粥样硬化,VCI的诊断依据《中国血管性认知障碍诊治指南(2019)》。使用多变量逻辑回归模型来探索IgGN-聚糖与VCI之间的关联。我们还通过典型相关分析(CCA)分析了IgGN-聚糖与VCI炎症状态之间的关系。
结果:通过多变量逻辑回归分析,8个聚糖和13个衍生性状反映减少的唾液酸化和半乳糖化和增加的二等分GlcNAc在调整混杂因子后在病例组和对照组之间显著不同(P<0.05,q<0.05)。同样,TNF-α的差异,IL-6、IL-10在校正混杂因素后,与对照组比较差异有统计学意义(P<0.05,q<0.05)。CCA结果显示,VCI相关初始N-聚糖与VCI相关炎症因子显著相关(r=0.272,P=0.004)。7种初始聚糖和炎症因子的组合AUC值(AUC组合=0.885)高于它们各自的值(AUC初始聚糖=0.818,AUC炎症因子=0.773)。
结论:结果表明,IgGN-聚糖所反映的唾液酸化和半乳糖化程度降低以及等分GlcNAc增加,可能通过促进IgG的促炎功能来影响动脉粥样硬化患者VCI的发生。IgGN-聚糖可以作为潜在的生物标志物来区分患有动脉粥样硬化的个体中的VCI。
BACKGROUND: Atherosclerosis is considered a crucial component in the pathogenesis of decreased cognitive function, as occurs in vascular cognitive impairment (VCI). Inflammation and the immune response play a significant role in the development of many chronic diseases. Immunoglobulin G (IgG) N-glycosylation has been implicated in the development of a variety of diseases by affecting the anti-inflammatory and proinflammatory responses of IgG. This study aimed to investigate the association between IgG N-glycosylation and VCI in a sample of patients with atherosclerosis through a
case-control study.
METHODS: We recruited a total of 330 patients with atherosclerosis to participate in this
case-control study, including 165 VCI patients and 165 sex- and age-matched participants with normal cognitive function. The plasma IgG N-glycans of participants were separated by ultrahigh-performance liquid chromatography. An enzyme-linked immunosorbent assay (ELISA) kit was used to determine the corresponding serum inflammatory factors. Atherosclerosis was diagnosed by carotid ultrasound, and the diagnosis of VCI was based on the \"Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment in China (2019)\". A multivariate logistic regression model was used to explore the association between IgG N-glycans and VCI. We also analyzed the relationship between IgG N-glycans and the inflammatory state of VCI through canonical correlation analysis (CCA).
RESULTS: Through the multivariate logistic regression analysis, 8 glycans and 13 derived traits reflecting decreased sialylation and galactosylation and increased bisecting GlcNAc significantly differed between the
case and control groups after adjusting for confounding factors (P < 0.05, q < 0.05). Similarly, the differences in TNF-α, IL-6, and IL-10 were statistically significant between the
case and control groups after adjusting for the effects of confounding factors (P < 0.05, q < 0.05). The CCA results showed that VCI-related initial N-glycans were significantly correlated with VCI-related inflammatory factors (r = 0.272, P = 0.004). The combined AUC value (AUC combined = 0.885) of 7 initial glycans and inflammatory factors was higher than their respective values (AUC initial glycans = 0.818, AUC inflammatory factors = 0.773).
CONCLUSIONS: The findings indicate that decreased sialylation and galactosylation and increased bisecting GlcNAc reflected by IgG N-glycans might affect the occurrence of VCI in patients with atherosclerosis though promoting the proinflammatory function of IgG. IgG N-glycans may serve as potential biomarkers to distinguish VCI in individuals with atherosclerosis.