中国健康成年人血清免疫球蛋白G糖基化特征参考区间的建立：在预测、预防和个性化医学框架下的全国性调查
Establishment of reference intervals for serum immunoglobulin G -glycosylation features in healthy Chinese adults: a nationwide survey in the framework of predictive, preventive, and personalized medicine.
作者信息
Liu Changyu, Wang Yinghao, Li Xingang, Xu Xiaojia, Xu Ruirui, Tian Cuihong, Chen Zhixian, Lu Xinxia, Li Yuejin, Wang Meng, Tang Zhaoyang, Chen Xueyu, Ding Guoyong, Tan Xuerui, Li Dong, Hou Haifeng, Wang Wei
机构信息
School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan, 250117 China.
The Second Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
出版信息
EPMA J. 2025 Aug 5;16(3):555-569. doi: 10.1007/s13167-025-00416-5. eCollection 2025 Sep.
BACKGROUND
Immunoglobulin G (IgG) glycosylation plays a vital role in the pathogenesis of autoimmune disorders, inflammatory diseases, and viral infections. While various models of serum IgG glycosylation have been developed to identify individuals at high risk for relevant diseases, reference intervals (RIs) for the levels of IgG glycans have not been established yet. Identifying RIs for serum IgG -glycans closely associated with biological aging and disease risk contributes to predictive, preventive, and personalized medicine (PPPM/3PM), which results in improvement of patients' outcomes, enhancement of healthcare efficiency, and in reducing burden of chronic diseases. This study is aimed at defining the age- and sex-specific RI in healthy Chinese adults.
METHODS
The healthy participants aged 18 years and above were recruited from Shandong and Guangdong provinces. Serum IgG glycans were analyzed using hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography (HILIC-UPLC), quantifying 24 glycan peaks (GPs). The 2.5th and 97.5th percentile reference limits for the glycans and their derived glycosylation features were used to define the 95 percentile of the reference distribution for glycan levels and derived glycosylation features.
RESULTS
A total of 927 participants (median age 52 years; 566 women and 361 men) were included. Of 24 glycan peaks, 14 differed significantly between sexes, and 18 varied by age. Age- and sex-specific RIs were independently calculated for all 24 glycan peaks. For key glycosylation features, the RIs were 87.37-97.63% for fucosylation, 11.08-21.69% for bisecting -acetylglucosamine (GlcNAc), 15.37-30.10% for sialylation, 15.93-41.91% for agalactosylation (G0), 22.60-36.93% for monogalactosylation (G1), and 10.46-26.99% for digalactosylation (G2). Individuals whose glycan indices locate in these RIs could be considered in a healthy glycosylation level.
CONCLUSIONS
This study identified and verified significant age- and sex-related differences in IgG glycosylation features and established RIs for IgG glycans in healthy Chinese adults. These RIs may serve as a useful benchmark for identifying individuals with abnormal glycosylation profiles. In PPPM/3PM, IgG -glycosylation RIs can predict disease risk, enable targeted prevention, and support personalized medical and health plans that consider age and gender.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13167-025-00416-5.
背景
免疫球蛋白G（IgG）糖基化在自身免疫性疾病、炎症性疾病和病毒感染的发病机制中起着至关重要的作用。虽然已经开发了各种血清IgG糖基化模型来识别相关疾病的高危个体，但IgG聚糖水平的参考区间（RIs）尚未建立。确定与生物衰老和疾病风险密切相关的血清IgG聚糖的RIs有助于实现预测性、预防性和个性化医学（PPPM/3PM），从而改善患者预后、提高医疗效率并减轻慢性病负担。本研究旨在确定健康中国成年人中年龄和性别特异性的RIs。
方法
从山东和广东省招募18岁及以上的健康参与者。使用超高效液相色谱亲水相互作用液相色谱法（HILIC-UPLC）分析血清IgG聚糖，定量24个聚糖峰（GPs）。聚糖及其衍生糖基化特征的第2.5和第97.5百分位数参考限值用于定义聚糖水平和衍生糖基化特征参考分布的第95百分位数。
结果
共纳入927名参与者（中位年龄52岁；566名女性和361名男性）。在24个聚糖峰中，14个在性别之间存在显著差异，18个随年龄变化。对所有24个聚糖峰独立计算年龄和性别特异性的RIs。对于关键糖基化特征，岩藻糖基化的RIs为87.37-97.63%，平分型N-乙酰葡糖胺（GlcNAc）的RIs为11.08-21.69%，唾液酸化的RIs为15.37-30.10%，无半乳糖基化（G0）的RIs为15.93-41.91%，单半乳糖基化（G1）的RIs为22.60-36.93%，双半乳糖基化（G2）的RIs为10.46-26.99%。聚糖指数位于这些RIs范围内的个体可被认为处于健康糖基化水平。
结论
本研究识别并验证了IgG糖基化特征中与年龄和性别相关的显著差异，并建立了健康中国成年人IgG聚糖的RIs。这些RIs可作为识别糖基化谱异常个体的有用基准。在PPPM/3PM中，IgG糖基化RIs可预测疾病风险、实现靶向预防，并支持考虑年龄和性别的个性化医疗和健康计划。
补充信息
在线版本包含可在10.1007/s13167-025-00416-5获取的补充材料。
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