系统性红斑狼疮患者的血清IgG糖链特征

Serum IgG Glycan Hallmarks of Systemic Lupus Erythematosus

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种发病机制不明、临床表型异质性大的自身免疫性疾病。目前已有的SLE血清生物标志物灵敏度或特异性有限,使得SLE的早期精准诊断存在困难。在本研究中,通过对389例SLE患者及304例健康对照者进行深入的糖组学分析,鉴定出血清免疫球蛋白G(IgG)上的两种N-糖链能够作为SLE的诊断生物标志物。在其他易与SLE混淆的系统性自身免疫性疾病(如类风湿性关节炎、原发性干燥综合征或系统性硬化症)中,这两种生物标志物没有出现显著变化,提示这两种N-糖链生物标志物对诊断SLE具有特异性。值得注意的是,这两种N-糖链生物标志物被证明是自身抗体非依赖性的,并且适用于所有阶段的SLE患者。基于片段特异性糖链分析和糖肽分析,发现这两种N-糖链生物标志物位于IgG上的Fc区域,并与疾病活动性密切相关。而酶学分析结果则提示,SLE患者体内一系列糖转移酶的失调可能是观察到的糖链产生变化的原因。研究结果为基于血清IgG糖基化的高效人群筛查和SLE潜在的新致病因素提供了新的思路。

Systemic lupus erythematosus(SLE)is a debilitating autoimmune disorder characterized by unknown pathogenesis and heterogeneous clinical manifestations.The current existing serum biomarkers for SLE have limited sensitivity or specificity,making early and precise diagnosis difficult.Here,we identified two N-glycans on serum immunoglobulin G(IgG)as excellent diagnostic biomarkers for SLE based on indepth glycomic analyses of 389 SLE patients and 304 healthy controls.These two N-glycan biomarkers are specific for diagnosing SLE,as no significant changes in these biomarkers were observed in other systemic autoimmune diseases that are easily confused with SLE,such as rheumatoid arthritis,primary Sjögren’s syndrome,or systemic sclerosis.Notably,the two N-glycan biomarkers proved to be autoantibody-independent and all-stage patient suitable.The two N-glycan biomarkers are demonstrated to be located on the Fc region based on fragment-specific glycan analysis and glycopeptide analysis,suggesting their close correlation with disease activity.Enzyme analyses revealed dysregulation of a series of glycotransferases in SLE,which might be responsible for the observed glycan alteration.Our findings provide insights into efficient population screening based on serum IgG glycosylation and potential new pathogenic factors of SLE.