Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID) Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.
Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Front Immunol. 2021 Jun 25;12:669137. doi: 10.3389/fimmu.2021.669137. eCollection 2021.
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease whose diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in PBC patients using high-throughput lectin microarrays technology.
Lectin microarray containing 56 lectins was used to detect and analyze the expression of serum IgG glycosylation in 99 PBC patients, 70 disease controls (DCs), and 38 healthy controls (HCs). Significant differences in PBC from control groups as well as across PBC subgroups positive for various autoantibodies were explored and verified by lectin blot technique.
Lectin microarray detection revealed that compared to DC and HC groups, the specific glycan level of serum IgG sialic acid in PBC patients was increased. For each PBC subgroup, glycan levels of IgG mannose and galactose were decreased in AMA-M2 positive PBC patients compared to the AMA-M2 negative group. IgG N-Acetylgalactosamine (GalNAc) and fucose were decreased in anti-sp100 positive patients. IgG galactose was increased in anti-gp210 positive patients. IgG mannose was decreased in ACA-positive patients. Although the difference in overall sialic acid level was not observed using lectin blot, all results among the above PBC subgroups were consistent with the results of the technique.
Lectin microarray is an effective and reliable technique for analyzing glycan structure. PBC patients positive for different autoantibody exhibits distinct glycan profile. Altered levels of glycosylation may be related to the occurrence and development of the disease, which could provide a direction for new biomarker identification.
原发性胆汁性胆管炎(PBC)是一种自身免疫性胆汁淤积性肝病,其诊断主要基于自身抗体检测。本研究旨在使用高通量凝集素微阵列技术研究 PBC 患者血清 IgG 的糖基化谱。
使用包含 56 种凝集素的凝集素微阵列检测和分析 99 例 PBC 患者、70 例疾病对照(DC)和 38 例健康对照(HC)的血清 IgG 糖基化表达。通过凝集素印迹技术探索和验证 PBC 与对照组之间以及 PBC 各自身抗体阳性亚组之间的差异。
凝集素微阵列检测显示,与 DC 和 HC 组相比,PBC 患者血清 IgG 唾液酸的特定糖基化水平增加。对于每个 PBC 亚组,与 AMA-M2 阴性组相比,AMA-M2 阳性 PBC 患者 IgG 甘露糖和半乳糖的糖基化水平降低。抗-sp100 阳性患者的 IgG N-乙酰半乳糖胺(GalNAc)和岩藻糖降低。抗-gp210 阳性患者的 IgG 半乳糖增加。ACA 阳性患者的 IgG 甘露糖减少。尽管凝集素印迹未观察到总体唾液酸水平的差异,但上述 PBC 亚组中的所有结果均与该技术的结果一致。
凝集素微阵列是分析糖基化结构的有效可靠技术。不同自身抗体阳性的 PBC 患者表现出不同的糖基化谱。糖基化水平的改变可能与疾病的发生和发展有关,这可能为新的生物标志物识别提供方向。