Takayasu 动脉炎患者血清 IgG 的糖基化谱改变。

Altered glycosylation profiles of serum IgG in Takayasu arteritis.

机构信息

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

出版信息

Eur J Med Res. 2023 Feb 8;28(1):69. doi: 10.1186/s40001-023-01035-4.

DOI:10.1186/s40001-023-01035-4

PMID:36755310

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906894/

Abstract

BACKGROUND

Takayasu arteritis (TAK) is an autoimmune inflammatory disorder with an undefined etiology. This study aimed to characterize the glycosylation profiles of serum immunoglobulin G (IgG) in patients with TAK.

METHODS

Lectin microarrays containing 56 types of lectins were used to detect the glycan levels of serum IgG in 164 patients with TAK, 128 patients with atherosclerosis used as disease controls (DCs), and 100 healthy controls (HCs). Differentially altered glycosylation patterns between TAK and control groups as well as between TAK subgroups were identified and further validated by lectin blot. The classification performance of the TAK-specific glycosylation change was measured by receiver-operating characteristic (ROC) curve analysis.

RESULTS

Lectin microarray analysis revealed significantly increased N-Acetylgalactosamine (GalNAc) levels in the TAK group compared to the DC and HC groups (all p < 0.01). For TAK subgroups, significantly decreased mannosylation was observed in patients with active TAK compared to patients with inactive disease (p < 0.01). These differences were validated by lectin blot. In addition, GalNAc levels exhibited a considerable potential for discriminating patients with TAK from patients with atherosclerosis, with an area under the curve of 0.749 (p < 0.001), a sensitivity of 71.7%, and a specificity of 73.8%.

CONCLUSIONS

Serum IgG in patients with TAK displayed disease-specific glycosylation alterations. Aberrant GalNAc glycosylation showed substantial value as a diagnostic biomarker. The potential proinflammatory properties of the abnormal glycans may provide new insights into the role of humoral immunity in the pathogenesis of TAK.

摘要

背景

Takayasu 动脉炎（TAK）是一种病因不明的自身免疫性炎症性疾病。本研究旨在描述 TAK 患者血清免疫球蛋白 G（IgG）的糖基化特征。

方法

使用包含 56 种凝集素的凝集素微阵列检测 164 例 TAK 患者、128 例动脉粥样硬化患者（DCs）和 100 例健康对照者（HCs）血清 IgG 的聚糖水平。通过凝集素印迹进一步验证和确认 TAK 组与对照组以及 TAK 亚组之间差异改变的糖基化模式。TAK 特异性糖基化变化的分类性能通过接受者操作特征（ROC）曲线分析来测量。

结果

凝集素微阵列分析显示，与 DC 和 HC 组相比，TAK 组 N-乙酰半乳糖胺（GalNAc）水平显著升高（均 p<0.01）。对于 TAK 亚组，与无活动 TAK 患者相比，活动 TAK 患者的甘露糖化显著降低（p<0.01）。这些差异通过凝集素印迹得到验证。此外，GalNAc 水平在区分 TAK 患者与动脉粥样硬化患者方面具有相当大的潜力，曲线下面积为 0.749（p<0.001），灵敏度为 71.7%，特异性为 73.8%。