Li Siting, Meng Jingjing, Xu Fang, Wang Qian, Tian Xinping, Li Mengtao, Zeng Xiaofeng, Hu Chaojun, Zheng Yuehong
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
J Clin Med. 2022 Sep 27;11(19):5727. doi: 10.3390/jcm11195727.
Inflammation plays a key role in the progression of atherosclerotic plaque for peripheral artery disease (PAD). Immunoglobulin G (IgG) glycosylation could modulate immunological effector functions and has been explored as biomarkers for various diseases.
Lectin microarray was applied to analyze the expression profile of serum IgG glycosylation in patients with lower-extremity peripheral artery disease (LEPAD), carotid artery stenosis (CAS), abdominal aortic aneurysm (AAA), and healthy controls. Lectin blot was performed to validate the differences.
SNA (Sambucus nigra agglutinin) binding (preferred sialic acid) was significantly higher in the LEPAD (3.21 ± 2.06) and AAA (3.34 ± 2.42) groups compared to the CAS (2.47 ± 1.45) group. Significantly higher binding levels of ConA (Concanavalin A) (preferred mannose) and PSA (Pisum sativum agglutinin) (preferred fucose) were also observed in LEPAD compared to CAS patients. Among LEPAD patients, a significant lower binding level of Black bean crude (preferred GalNAc) was present for dyslipidemia patients. A higher binding level of MNA-M (Morniga M agglutinin) (preferred Mannose) and Jacalin-AIA (Artocarpus integrifolia agglutinin) (preferred Galβ3GalNAc) was observed for Fontaine severe patients. Higher binding levels of PHA-E (Phaseolus vulgaris Erythroagglutinin) and PHA-L (Phaseolus vulgaris Leucoagglutinin) (preferred Galβ4GlcNAc) were observed for diabetic patients, and higher binding of ASA (Allium sativum agglutinin) (preferred Mannose) was present in patients with hypertension. The level of high-sensitivity C-reactive protein (hsCRP) was positively associated with LTL (Lotus tetragonolobus lectin) ( 0.44), PSA ( 0.44), LCA (Lens Culinaris agglutinin) ( = 0.39), SNA ( 0.57), and CSA (Cytisus sscoparius agglutinin) ( 0.56). For CAS, symptomatic patients had lower binding levels of AAL (Aleuria aurantia lectin) (preferred fucose) and IAA (Iberis amara agglutinin) (preferred GalNAc). Blood total cholesterol level was positively associated with SNA-I ( 0.36) and SBA (Soybean agglutinin) ( 0.35). Creatinine levels were positively associated with lectins including, but not limited to, MNA-M ( 0.42), CSA ( 0.45), GHA (Glechoma hederacea agglutinin) ( 0.42), and MNA-G (Morniga G agglutinin) ( 0.45).
LEPAD patients had increased IgG binding levels of SNA and ConA compared to CAS, which could provide potential diagnostic value. Fontaine severity was associated with Mannose-rich IgG N-glycan, while diabetic LEPAD correlated with bisecting GlcNAc. The levels of hsCRP and creatinine were positively associated with IgG fucosylation and galactosylation. Changes in IgG glycosylation may play important roles in PAD pathogenesis and progression.
炎症在周围动脉疾病（PAD）的动脉粥样硬化斑块进展中起关键作用。免疫球蛋白G（IgG）糖基化可调节免疫效应功能，并已被探索作为多种疾病的生物标志物。
应用凝集素微阵列分析下肢周围动脉疾病（LEPAD）、颈动脉狭窄（CAS）、腹主动脉瘤（AAA）患者及健康对照者血清IgG糖基化的表达谱。进行凝集素印迹以验证差异。
与CAS组（2.47±1.45）相比，LEPAD组（3.21±2.06）和AAA组（3.34±2.42）中SNA（黑接骨木凝集素，偏好唾液酸）结合显著更高。与CAS患者相比，LEPAD患者中ConA（刀豆球蛋白A，偏好甘露糖）和PSA（豌豆凝集素，偏好岩藻糖）的结合水平也显著更高。在LEPAD患者中，血脂异常患者的黑豆粗提物（偏好N-乙酰半乳糖胺）结合水平显著更低。对于Fontaine重度患者，观察到MNA-M（莫尼加M凝集素，偏好甘露糖）和Jackalin-AIA（菠萝蜜凝集素，偏好Galβ3GalNAc）的结合水平更高。糖尿病患者中观察到PHA-E（菜豆红细胞凝集素）和PHA-L（菜豆白细胞凝集素，偏好Galβ4GlcNAc）的结合水平更高，高血压患者中ASA（大蒜凝集素，偏好甘露糖）的结合更高。高敏C反应蛋白（hsCRP）水平与LTL（四角豆凝集素）（r = 0.44）、PSA（r = 0.44）、LCA（扁豆凝集素）（r = 0.39）、SNA（r = 0.57）和CSA（金雀花凝集素）（r = 0.56）呈正相关。对于CAS，有症状患者的AAL（橙黄网孢盘菌凝集素，偏好岩藻糖）和IAA（屈曲花凝集素，偏好N-乙酰半乳糖胺）结合水平更低。血液总胆固醇水平与SNA-I（r = 0.36）和SBA（大豆凝集素）（r = 0.35）呈正相关。肌酐水平与多种凝集素呈正相关，包括但不限于MNA-M（r = 0.42）、CSA（r = 0.45）、GHA（连钱草凝集素）（r = 0.42）和MNA-G（莫尼加G凝集素）（r = 0.45）。
与CAS相比，LEPAD患者的SNA和ConA的IgG结合水平升高，这可能提供潜在的诊断价值。Fontaine严重程度与富含甘露糖的IgG N-聚糖相关，而糖尿病性LEPAD与平分型GlcNAc相关。hsCRP和肌酐水平与IgG岩藻糖基化和半乳糖基化呈正相关。IgG糖基化的变化可能在PAD发病机制和进展中起重要作用。
