Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study

• DOI: 10.3389/fimmu.2023.1257906
• Publication Date: 2023-09-21T19:30:04Z
• Authors: Xinxia Lu; Liangao Wang; Meng Wang; Yuejin Li; Qinqin Zhao; Yanjun Shi; Yujing Zhang; Yingjie Wang; Wei Wang; Long Ji; Haifeng Hou; Dong Li
• Keywords: lupus nephritis; Glycosylation; Immunology; 610; biomarkers; Diseases; N-glycosylation; RC581-607; Lupus Nephritis; 3. Good health; immunoglobulin G; Immune System Diseases; inflammation; Polysaccharides; Immunoglobulin G; Case-Control Studies; Medicine and Health Sciences; Humans; Lupus Erythematosus, Systemic; Female; Immunologic diseases. Allergy

BackgroundLupus 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.MethodsThis 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.ResultsThere 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 (P < 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 (P < 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).ConclusionOur 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.