School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Jinshan District Center for Disease Control and Prevention, Shanghai, China.
Front Immunol. 2023 Sep 21;14:1257906. doi: 10.3389/fimmu.2023.1257906. eCollection 2023.
BACKGROUND: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. METHODS: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated. RESULTS: There were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN ( < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients ( < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858). CONCLUSION: Our findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.
背景：狼疮肾炎（LN）是系统性红斑狼疮（SLE）的一个重要并发症，对指导治疗具有重要的临床意义。免疫球蛋白 G（IgG）的 N-糖基化通过影响抗炎和促炎反应的平衡，在 SLE 的发展中起关键作用。本研究旨在评估 IgG N-糖基化在女性 SLE 患者中诊断 LN 的性能。
方法：本病例对照研究纳入了 188 名女性 SLE 患者，其中 94 例为 LN 患者，94 例为年龄匹配的无 LN 患者。采用亲水作用色谱-超高效液相色谱（HILIC-UPLC）检测血浆 IgG N-糖肽谱。使用多变量 logistic 回归模型探讨 IgG N-聚糖与 LN 的关系。利用有统计学意义的糖肽以及人口统计学因素建立诊断模型。通过受试者工作特征（ROC）曲线分析评估 IgG N-聚糖在诊断 LN 中的性能，并计算曲线下面积（AUC）及其 95%置信区间（CI）。
结果：LN 患者与无 LN 患者之间有 9 种初始糖（GP2、GP4、GP6、GP8、GP10、GP14、GP16、GP18 和 GP23）存在显著差异（<0.05）。LN 患者的唾液酸化、半乳糖基化和岩藻糖化聚糖水平明显低于对照组，而双乙酰氨基葡萄糖（GlcNAc）聚糖水平升高（<0.05）。GP8、GP10、GP18 和贫血被纳入我们的诊断模型，该模型在区分 LN 女性 SLE 患者与非 LN 患者方面表现良好（AUC=0.792，95%CI：0.727 至 0.858）。
结论：我们的研究结果表明，唾液酸化、半乳糖基化和核心岩藻糖基化减少以及双乙酰氨基葡萄糖增加可能通过上调 IgG 的促炎反应在 LN 的发展中起作用。IgG N-聚糖可以作为潜在的生物标志物，用于区分 SLE 患者中的 LN 个体。
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