Establishment of reference intervals for serum immunoglobulin G N-glycosylation features in healthy Chinese adults: a nationwide survey in the framework of predictive, preventive, and personalized medicine.
{"title":"Establishment of reference intervals for serum immunoglobulin G <i>N</i>-glycosylation features in healthy Chinese adults: a nationwide survey in the framework of predictive, preventive, and personalized medicine.","authors":"Changyu Liu, Yinghao Wang, Xingang Li, Xiaojia Xu, Ruirui Xu, Cuihong Tian, Zhixian Chen, Xinxia Lu, Yuejin Li, Meng Wang, Zhaoyang Tang, Xueyu Chen, Guoyong Ding, Xuerui Tan, Dong Li, Haifeng Hou, Wei Wang","doi":"10.1007/s13167-025-00416-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin G (IgG) <i>N-</i>glycosylation plays a vital role in the pathogenesis of autoimmune disorders, inflammatory diseases, and viral infections. While various models of serum IgG <i>N-</i>glycosylation have been developed to identify individuals at high risk for relevant diseases, reference intervals (RIs) for the levels of IgG <i>N-</i>glycans have not been established yet. Identifying RIs for serum IgG <i>N</i>-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.</p><p><strong>Methods: </strong>The healthy participants aged 18 years and above were recruited from Shandong and Guangdong provinces. Serum IgG <i>N-</i>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.</p><p><strong>Results: </strong>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 <i>N</i>-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.</p><p><strong>Conclusions: </strong>This study identified and verified significant age- and sex-related differences in IgG <i>N-</i>glycosylation features and established RIs for IgG <i>N-</i>glycans in healthy Chinese adults. These RIs may serve as a useful benchmark for identifying individuals with abnormal glycosylation profiles. In PPPM/3PM, IgG <i>N</i>-glycosylation RIs can predict disease risk, enable targeted prevention, and support personalized medical and health plans that consider age and gender.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-025-00416-5.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 3","pages":"555-569"},"PeriodicalIF":5.9000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423389/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The EPMA journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s13167-025-00416-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Immunoglobulin G (IgG) N-glycosylation plays a vital role in the pathogenesis of autoimmune disorders, inflammatory diseases, and viral infections. While various models of serum IgG N-glycosylation have been developed to identify individuals at high risk for relevant diseases, reference intervals (RIs) for the levels of IgG N-glycans have not been established yet. Identifying RIs for serum IgG N-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 N-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 N-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 N-glycosylation features and established RIs for IgG N-glycans in healthy Chinese adults. These RIs may serve as a useful benchmark for identifying individuals with abnormal glycosylation profiles. In PPPM/3PM, IgG N-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.
中国健康成人血清免疫球蛋白G - n -糖基化特征参考区间的建立：一项预测、预防和个性化医疗框架下的全国性调查
背景：免疫球蛋白G (IgG) n -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。虽然已经建立了各种血清IgG n -糖基化模型来识别相关疾病的高危人群，但IgG n -聚糖水平的参考区间（RIs）尚未建立。识别与生物衰老和疾病风险密切相关的血清IgG n -聚糖RIs有助于预测、预防和个性化医疗（PPPM/3PM），从而改善患者预后，提高医疗保健效率，减轻慢性疾病负担。本研究旨在确定中国健康成人的年龄和性别特异性RI。方法：从山东和广东两省招募年龄在18岁及以上的健康受试者。采用超高效液相色谱（HILIC-UPLC）亲水相互作用液相色谱分析血清IgG n -聚糖，定量测定24个聚糖峰（GPs）。采用多糖及其衍生糖基化特征的2.5和97.5百分位参考限来确定多糖水平及其衍生糖基化特征的参考分布的95百分位。结果：共纳入927名参与者（中位年龄52岁，女性566名，男性361名）。在24个聚糖峰中，有14个存在显著的性别差异，18个存在年龄差异。所有24个聚糖峰的年龄和性别特异性RIs被独立计算。对于关键的糖基化特征，集中化的RIs为87.37 ~ 97.63%，分割n -乙酰氨基葡萄糖（GlcNAc）的RIs为11.08 ~ 21.69%，唾液化的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%。糖基化指数在这些RIs范围内的个体可被认为处于健康的糖基化水平。结论：本研究发现并验证了IgG n -糖基化特征在中国健康成人中的显著年龄和性别相关差异，并建立了IgG n -聚糖的RIs。这些RIs可以作为识别异常糖基化谱个体的有用基准。在PPPM/3PM中，IgG n -糖基化RIs可以预测疾病风险，实现有针对性的预防，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：在线版本包含补充资料，可在10.1007/s13167-025-00416-5获得。
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